Biology subjects

Lauderdale, J. D.

Publications and source records attributed to Lauderdale, J. D..

7 recordsLinked to original sources

bioRxiv2024

Decreased GABA levels during development result in increased connectivity in the larval zebrafish tectum

{gamma}-aminobutyric acid (GABA) is an abundant neurotransmitter that plays multiple roles in the vertebrate central nervous system (CNS). In the early developing CNS, GABAergic signaling acts to depolarize cells. It mediates several aspects of neural development, including cell proliferation, neuronal migration, neurite growth, and synapse formation, as well as the development of critical periods. Later in CNS development, GABAergic signaling acts in an inhibitory manner when it becomes the predominant inhibitory neurotransmitter in the brain. This behavior switch occurs due to changes in chloride/cation transporter expression. Abnormalities of GABAergic signaling appear to underlie several human neurological conditions, including seizure disorders. However, the impact of reduced GABAergic signaling on brain development has been challenging to study in mammals. Here we take advantage of zebrafish and light sheet imaging to assess the impact of reduced GABAergic signaling on the functional circuitry in the larval zebrafish optic tectum. Zebrafish have three gad genes: two gad1 paralogs known as gad1a and gad1b, and gad2. The gad1b and gad2 genes are expressed in the developing optic tectum. Null mutations in gad1b significantly reduce GABA levels in the brain and increase electrophysiological activity in the optic tectum. Fast light sheet imaging of genetically encoded calcium indicator (GCaMP)-expressing gab1b null larval zebrafish revealed patterns of neural activity that were different than either gad1b-normal larvae or gad1b-normal larvae acutely exposed to pentylenetetrazole (PTZ). These results demonstrate that reduced GABAergic signaling during development increases functional connectivity and concomitantly hyper-synchronization of neuronal networks. Significance StatementUnderstanding the impact of reduced GABAergic signaling on vertebrate brain development and function will help elucidate the etiology of seizure initiation and propagation and other neurological disorders due to the altered formation of neural circuits. Here, we used fast light sheet imaging of larval zebrafish that neuronally expressed a genetically encoded calcium indicator (GCaMP) to assess the impact of reduced GABA levels through null mutation of gad1b during brain development. We show that reduced GABA levels during development result in increased functional connectivity in the brain.

neuroscience↗

bioRxiv2023

Maturation and Refinement of the Maculae and Foveae in the Anolis sagrei lizard

In primates, the fovea is a pit in the center of the macula, which is a region of the retina with a high concentration of cone photoreceptor cells that accounts for a large degree of visual acuity in primates. The maturation of this primate visual acuity area is characterized by the shallowing and widening of the foveal pit, a decrease in the diameter of the rod-free zone, and packing of photoreceptor cells more densely into this area of the retina, which occurs sometime after birth. Maturation occurs concurrently with progressing age and development, which further correlates with increasing eye size, retinal length, and retinal area. These observations have led to the hypothesis that the maturation of the fovea might be a function of mechanical variables that remodel the retina. However, this has never been explored outside of primates. Here, we take advantage of the Anolis sagrei lizard, which has a bifoveated retina, to study maturation of the fovea and macula. Eyes were collected from male and female lizards from five different age groups - hatchling, 2-month, 4-month, 6-month, and adult. We found that Anolis maculae undergo a maturation process somewhat different than what has been observed in primates. Anole macular diameters actually increase in size and undergo minimal photoreceptor cell packing, possessing a near complete complement of these cells at the time of hatching. As the anole eye expands, foveal centers experience little change in overall retina cell density with most cell redistribution occurring at the macular borders and peripheral retina areas. O_FIG O_LINKSMALLFIG WIDTH=200 HEIGHT=200 SRC="FIGDIR/small/529081v1_ufig1.gif" ALT="Figure 1"> View larger version (73K): org.highwire.dtl.DTLVardef@effd8dorg.highwire.dtl.DTLVardef@1ef65b3org.highwire.dtl.DTLVardef@1fde14dorg.highwire.dtl.DTLVardef@d2c0b2_HPS_FORMAT_FIGEXP M_FIG C_FIG Highlights- Foveal and retinal refinement occurs post-hatching into adulthood in anoles. - The temporal pit shallows and widens, whereas central pit morphology remains relatively constant with age. - Retina cell number within a section decreases as the eye grows larger with age. - Anole macular diameter increases from hatching to adult but does not increase proportionately to overall eye growth.

developmental biology↗

bioRxiv2021

Development and retinal remodeling in the brown anole lizard (Anolis sagrei)

BackgroundThe fovea, a pit in the retina, is believed to be important for high-acuity vision and is a feature found in the eyes of humans and a limited number of vertebrate species that include certain primates, birds, lizards, and fish. At present, model systems currently used for ocular research lack a foveated retina and studies investigating fovea development have largely been limited to histological and molecular studies in primates. As a result, progress towards understanding the mechanisms involved in regulating fovea development in humans is limited and is completely lacking in other, non-primate, vertebrates. To address this knowledge gap, we provide here a detailed histological atlas of retina and fovea development in the bifoveated Anolis sagrei lizard, a novel reptile model for fovea research. We also further test the hypothesis that retinal remodeling, which leads to fovea formation and photoreceptor cell packing, is related to asymmetric changes in eye shape. ResultsAnole retina development follows the conventional spatiotemporal patterning observed in most vertebrates, where retina neurogenesis begins within the central retina, progresses throughout the temporal retina, and concludes in the nasal retina. One exception to this general rule is that areas that give rise to the fovea undergo retina differentiation prior to the rest of the retina. We find that retina thickness changes dynamically during periods of ocular elongation and retraction. During periods of ocular elongation, the retina thins, while during retraction it becomes thicker. Ganglion cell layer mounding is also observed in the temporal fovea region just prior to pit formation. ConclusionsAnole retina development parallels that of humans, including the onset and progression of retinal neurogenesis followed by changes in ocular shape and retinal remodeling that leads to pit formation in the retina. We propose that anoles are an excellent model system for fovea development research. Key FindingsO_LIRetina mounding that occurs in foveal areas prior to retinal differentiation progressively disappear as foveal regions of the eye elongate. C_LIO_LIThe central and temporal foveal areas undergo retina differentiation before the rest of the retina. C_LIO_LIGCL mounding prior to pit formation occurs in the area of the temporal fovea but not the central fovea. C_LIO_LIWhen the eye is experiencing ocular retraction, photoreceptor cell packing, and pit formation are observed within foveal regions. C_LI

developmental biology↗

bioRxiv2021

Anterior eye development in the brown anole, Anolis sagrei

BackgroundAnterior eye development has been explored in different vertebrate species ranging from fish to mammals. However, missing from this diverse group is a representative of reptiles. A promising candidate to fill this void is the brown anole, Anolis sagrei, which is easily raised in the laboratory and for which genome editing techniques exist. Here we provide a detailed histological analysis of the development of the anterior structures of the eye in A. sagrei, which include the cornea, iris, ciliary body, lens, trabecular meshwork, and sclera ossicles. ResultsDevelopment of the anterior segment in Anoles proceeds as for other vertebrates with the lens forming first followed by the cornea, then the iris, ciliary body, trabecular meshwork, and sclera ossicles. The onset of these latter structures occurs first temporally than nasally. Unlike the eyes of mammals and birds, anoles possess a remarkably thin cornea, flat ciliary body, and a trabecular meshwork that lacks an obvious Schlemms canal. ConclusionsThis study highlights several features present in anoles and represents an important step towards understanding reptile eye development. Key FindingsO_LIThe anole cornea epithelium is thin, composed mainly of a single basal cell layer. C_LIO_LIThe ciliary body lacks a ciliary process. C_LIO_LIIris and ciliary body formation occur in a spatiotemporal fashion, developing first temporally then nasally. C_LIO_LIThe anole trabecular meshwork is composed of a spongiform tissue and lacks a Schlemms canal. C_LI

developmental biology↗

bioRxiv2021

Ocular elongation and retraction in foveated reptiles

BackgroundPronounced asymmetric changes in ocular globe size during eye development have been observed in a number of species ranging from humans to lizards. In contrast, largely symmetric changes in globe size have been described for other species like rodents. We propose that asymmetric changes in the three-dimensional structure of the developing eye correlate with the types of retinal remodeling needed to produce areas of high photoreceptor density. To test this idea, we systematically examined three-dimensional aspects of globe size as a function of eye development in the bifoveated brown anole, Anolis sagrei. ResultsDuring embryonic development, the anole eye undergoes dynamic changes in ocular shape. Initially spherical, the eye elongates in the presumptive foveal regions of the retina and then proceeds through a period of retraction that returns the eye to its spherical shape. During this period of retraction, pit formation and photoreceptor cell packing are observed. We found a similar pattern of elongation and retraction associated with the single fovea of the veiled chameleon, Chamaeleo calyptratus. ConclusionsThese results, together with those reported for other foveated species, support the idea that areas of high photoreceptor packing occur in regions where the ocular globe asymmetrically elongates and retracts during development. Key FindingsO_LIThe eyes of the brown anole, Anolis sagrei, and veiled chameleon, Chamaeleo calyptratus undergo dynamic asymmetrical changes in ocular shape during development. C_LIO_LIIn both species, asymmetric elongation and retraction of the ocular globe is associated with fovea morphogenesis. C_LIO_LIPit formation and photoreceptor cell packing in the foveal area occur when the corresponding region of the ocular globe is retracting relative to adjacent regions. C_LI

developmental biology↗

bioRxiv2020

Increased TSH-producing cells in the pituitary gland of Pax6 haploinsufficient mice

Aniridia is a congenital condition characterized by absence of iris and is caused by a semidominant mutation in the transcription factor encoded by the PAX6 gene. Although ocular phenotypes of this disorder are well characterized, recent studies report that individuals with aniridia have a higher propensity for obesity, infertility, polycystic ovarian disease, and severe eczema compared to their Pax6-normal siblings. These symptoms collectively suggest an underlying endocrine disturbance related to haploinsufficient levels of Pax6. In mice, during development, Pax6 expression in the pituitary gland begins at E9.0 in the primordial anterior pituitary gland (Rathkes Pouch). This expression becomes restricted to the dorsal anterior pituitary by E11.5, but is expressed throughout the anterior lobe by E14.5, and remains through adulthood. It is possible that a reduction in Pax6 could result in a change in pituitary hormone levels or cell numbers, which may explain symptoms experienced by aniridics. Using the Small eye mouse model, we find that Pax6 reduction results in a decrease in GH-producing cells and an increase in TSH-producing cells in neonate mice, with the TSH increase continuing into adulthood. Adult Pax6 haploinsufficient mice also have an increase in anterior pituitary volume and weigh significantly less than their wild-type littermates. Furthermore, we show that the increase in TSH-producing cells leads to an increase in thyroxin (T4) in mutant mice, although tri-iodothyronine (T3) levels remain unchanged. These findings present a new role for Pax6 in the endocrine system, which serves to refine our current understanding of Pax6 in endocrine development and maintenance and provides new avenues for investigating endocrine-related symptomatology in aniridia.

developmental biology↗

bioRxiv2019

CRISPR-Cas9 Gene Editing in Lizards Through Microinjection of Unfertilized Oocytes

CRISPR-Cas9 mediated gene editing has enabled the direct manipulation of gene function in many species. However, the reproductive biology of reptiles presents unique barriers for the use of this technology, and there are currently no reptiles with effective methods for targeted mutagenesis. Here we present a new approach that enables the efficient production of CRISPR-Cas9 induced mutations in Anolis lizards, an important model for studies of reptile evolution and development.

genetics↗