Biology subjects

Corbin, T. J.

Publications and source records attributed to Corbin, T. J..

5 recordsLinked to original sources

bioRxiv2026

Nucleolar Dynamics During Oogenesis

Ribosome biogenesis is a conserved and highly regulated process that starts in the nucleolus, a membrane-less multi-phase organelle. Although the architecture of the nucleolus is known to change due to perturbations, how nucleolar organization is modulated during physiological processes to meet changing translational demands remains unclear. Here, we use zebrafish oogenesis as a developmental context requiring a rapid expansion of translational capacity to investigate the regulation of nucleolar architecture. We show nucleoli undergo coordinated changes in number, size, subnuclear localization, and layering throughout oogenesis. We further demonstrate that nucleoli form around extrachromosomal DNA circles that contain the rDNA locus. Notably, mouse oocytes undergo similar developmental changes in nucleolar layering and phase organization, indicating that remodeling of nucleolar condensates is a conserved feature of oogenesis. These findings reveal previously unexplored regulation of nucleolar architecture as developmental adaptations to changing biosynthetic needs.

developmental biology↗

bioRxiv2024

A new genetically tractable non-vertebrate system to study complete camera-type eye regeneration

Camera-type eyes are complex sensory organs susceptible to irreversible damage. Their repair is difficult to study due to the paucity of camera-type eye regeneration models. Identifying a genetically tractable organism with the ability to fully regenerate complete camera-type eyes would help overcome this difficulty. Here, we introduce the apple snail Pomacea canaliculata, capable of full regeneration of camera-type eyes even after complete resection. We defined anatomical components of P. canaliculata eyes and genes expressed during crucial steps of their regeneration. By exploiting the unique features of this organism, we successfully established the first stable mutant lines in apple snails. Our studies revealed that, akin to humans, pax6 is indispensable for eye development in apple snails, establishing this as a research organism to unravel the mechanisms of camera-type eye regeneration. This work expands our understanding of complex sensory organ regeneration and offers new ways to explore this process.

developmental biology↗

bioRxiv2022

rRNA transcription is integral to liquid-liquid phase separation and maintenance of nucleolar structure

Beginning with transcription of ribosomal RNA (rRNA) by RNA Polymerase (Pol) I in the nucleolus, ribosome biogenesis is intimately tied to cell growth and proliferation. Perturbation of ribosome biogenesis has been previously shown to affect nucleolar structure, yet the underlying mechanism is unknown. We generated loss-of-function mouse mutants of Pol I subunits, Polr1a, Polr1b, Polr1c and Polr1d, thereby genetically inhibiting rRNA transcription and ribosome biogenesis. Pol I mutant embryos are preimplantation lethal and have fewer nucleoli. Using hiPSCs triple labeled for the three nucleolar compartments, we observe two phenotypes upon Pol I inhibition: a single condensed nucleolus, and fragmented nucleoli. We find that when rRNA transcription is inhibited, the viscosity of the granular compartment of the nucleolus is increased disrupting its liquid-liquid phase separation properties, which results in a condensed nucleolus. Taken together, our data suggests that Pol I function and rRNA transcription are required for maintaining nucleolar structure and integrity.

developmental biology↗

bioRxiv2022

Molecular Control of Circuit Plasticity and the Permanence of Imprinted Odor Memory

Behavioral imprinting is a distinct form of learning that has a lifelong impact on social interactions and affectional behaviors1-4. Unlike other forms of memory, imprinting does not require conspicuous association of stimuli; exposure per se appears sufficient to induce memories that neither undergo extinction nor are altered by experience later in life. The site of storage of imprinted memory and the mechanisms that control its formation and permanence are unknown. Here we uncover a molecular mechanism that controls olfactory imprinting, which underlies behaviors including kin and nest recognition, maternal attachment, and homing5-10. We show that odor exposure during the perinatal period converts an innately aversive odor into a homing signal. The behavioral change is associated with odor-induced changes in the projection patterns of olfactory sensory neuron (OSN) expressing the cognate receptors for the exposed odor. We show that the Wnt signaling receptor Frizzled1 (Fzd1) acts as a master regulator of the critical period of OSN development and is responsible for closing the critical period to prevent further changes in the neural circuit. In Fzd1 knockout mice axon projection patterns are continually modified by sensory experience. As Fzd1 knockout abolishes the developmental critical period, it also abolishes odor imprinting. Specific knockout of Fzd1 in the OSNs have the same effect. Mechanistically, Fzd1 controls the critical period through an autoregulated shutdown and by controlling an activity-driven regulon in the OSNs. The transient expression and the subsequent downregulation of Fzd1 leads to the irreversible closure of the critical period to lock in circuits established during the critical period. The evidence suggests that imprinted odor memory is stored in the patterns of connectivity at the first synapse in the olfactory bulb. Early odor experience induces changes in the OSN projection to alter connectivity with innate circuits to establish a life-long memory.

neuroscience↗

bioRxiv2020

CRISPR-Cas13d induces efficient mRNA knock-down in animal embryos

Early embryonic development is driven exclusively by maternal gene products deposited into the oocyte. Although critical in establishing early developmental programs, maternal gene functions have remained elusive due to a paucity of techniques for their systematic disruption and assessment. CRISPR-Cas13 systems have recently been employed to induce RNA degradation in yeast, plants and mammalian cell lines. However, no systematic study of the potential of Cas13 has been carried out in an animal system. Here, we show that CRISPR-Cas13d is an effective and precise system to deplete specific mRNA transcripts in zebrafish embryos. We demonstrate that both zygotically-expressed and maternally-provided transcripts are efficiently targeted, resulting in an 80% average decrease in transcript level and the recapitulation of well-known embryonic phenotypes. Moreover, we show that this system can be used in medaka, killifish and mouse embryos. Altogether our results demonstrate that CRISPR-Cas13d is an efficient knock-down platform to interrogate gene function in animal embryos.

developmental biology↗