Biology subjects

Fekete, C.

Publications and source records attributed to Fekete, C..

4 recordsLinked to original sources

bioRxiv2026

Brain-wide mapping of proglucagon expression in mice identifies fasting-responsive GLP-1 neurons in the posterior hypothalamic nucleus

ObjectiveGlucagon-like peptide-1 (GLP-1), a peptide neurotransmitter in the brain, is synthesized from proglucagon, encoded by the glucagon gene (Gcg). Besides medullary GLP-1 neurons, Gcg-expressing neuron populations were identified in the olfactory bulb and basolateral amygdala. However, several lines of evidence suggest that additional Gcg neuron populations might exist. MethodsWe conducted a brain-wide mapping of Gcg-expressing cells by fluorescent in situ hybridization in C57BL/6J and FVB/Ant mice. Proglucagon and GLP-1 expression were studied with immunofluorescence. We characterized a Gcg-Cre;tdTomato mouse line and studied the expression of proglucagon-processing enzymes in Gcg-expressing neuron populations. We used adeno-associated virus-mediated tracing in Gcg-Cre mice to map the projections of hypothalamic Gcg neurons. ResultsGcg-expressing neuron populations were identified in the olfactory bulb, claustrum, piriform cortex, basolateral amygdala, posterior hippocampus, posterior hypothalamic nucleus (PH), periaqueductal gray/dorsal raphe, and dorsal nucleus of the lateral lemniscus. These neurons express lower Gcg mRNA levels than medullary GLP-1 neurons. Proglucagon and GLP-1-immunoreactivity (C-terminus) were detected in almost all Gcg-expressing neuron populations, along with the mRNAs for prohormone convertases 1/3 and 2, enzymes generating GLP-1 or glucagon, respectively. Fasting markedly increased Gcg mRNA, proglucagon and GLP-1 synthesis in the PH. PH Gcg neurons project densely to the ventral and intermediate lateral septum, preoptic region, ventrolateral preoptic nucleus, lateral hypothalamus and zona incerta, establishing close contacts with both GLP-1 receptor-positive and -negative neurons. ConclusionsProglucagon is expressed in 9 distinct neuron populations. Feeding status regulates GLP-1 synthesis in PH neurons that likely control feeding- or energy balance-related functions.

neuroscience↗

bioRxiv2026

Modulation of Avian Iridescence via Malanogenesis

The iridescent colors of birds originate in nanoscale feather structures that interact with light. Although the physical principles governing avian iridescence are well-established, the molecular mechanisms assembling these nanostructures into photonic materials remain unknown. Here, we integrated genomic, cellular, and optical approaches to investigate the molecular basis of iridescent color formation in birds. We leveraged mutations that arose in the domesticated Indian peafowl and natural color variation in wild birds. In peafowl, we identified eight genes underlying gains, losses, and shifts of iridescence, whereas in two wild species, we used single-cell transcriptomics to profile asymmetric feathers in which iridescent and non-iridescent barbules develop on opposite sides of the same feather. We found that all peafowl mutations mapped to melanogenesis genes, showing that variation in this pathway can modify diverse geometric features of feather photonic nanostructures. Mutations altering melanin composition collapsed multilayered photonic systems and yielded non-iridescent tissues, whereas changes in melanosome abundance, elongation, or deposition timing generated multilayer architectures with variable periodicity and color. We further show in peafowl that transitions from non-iridescent to iridescent plumage were associated with single-nucleotide mutations in a melanogenesis gene, suggesting that, in species already capable of forming multilayered nanostructures, iridescence can be gained by relatively small genetic changes. Single-cell transcriptomes from wild species also supported extensive melanocyte-centered regulatory rewiring associated with iridescence, including changes in melanosome maturation, trafficking, and intercellular signaling. Together, these results show that the nanoscale order underlying iridescence is developmentally plastic and highly responsive to the melanogenic environment. Significance StatementBird feathers can produce brilliant, shifting colors, but how these colors form during development has remained poorly understood. By comparing the genomes of color variants of domesticated peafowl and transcriptomes during feather development in wild birds, and combining these with chemical and optical analyses, we show that mutations in genes associated with melanogenesis can profoundly alter the amount, shape, and arrangement of the melanin granules inside feathers that interact with light and produce iridescence. These changes can switch feather appearance between dull and iridescent, or generate entirely new colors by restructuring how those granules are layered at the microscopic scale. Our results reveal a direct and flexible link between pigment production and the physical structures that generate iridescence in birds.

evolutionary biology↗

bioRxiv2023

Estrogen-dependent development and transcriptome regulation of the lateral septal kisspeptin system

While hypothalamic kisspeptin (KP) neurons play well-established roles in the estrogen-dependent regulation of reproduction, little is known about extrahypothalamic KP-producing (KPLS) neurons of the lateral septum. Our studies on Kiss1-Cre/ZsGreen transgenic mice revealed that KP expression in the LS is linked to puberty and estrogen receptor signaling and neurons reach higher numbers in females. Viral tracing uncovered that KPLS axons abundantly innervate gonadotropin-releasing hormone neurons, the hypothalamic supramammillary nucleus and various limbic structures. RNA-Seq analysis of laser-microdissected KPLS neurons revealed a unique transcriptome profile containing markers of GABAergic and peptidergic (Penk, Cartpt, Vgf) cotransmission and 571 estrogen-dependent transcripts. Immunohistochemical evidence for homologous neurons in the post mortem human brain indicate that the KPLS neurons may contribute to evolutionarily conserved regulatory mechanisms. The KPLS system now emerges as a novel player in the estrogen-dependent control of gonadotropin-releasing hormone neurons and currently unknown hypothalamic and limbic functions requiring clarification.

neuroscience↗

bioRxiv2022

A PATHWAY FOR T3 SIGNALING IN THE BRAIN TO IMPROVE THE VARIABLE EFFECTIVENESS OF THERAPY WITH L-T4

The effectiveness of therapy for hypothyroidism with levothyroxine (L-T4) depends on patients ability to activate T4 to T3 --altered in carriers of a common deiodinase polymorphism (Thr92Ala-DIO2). Some patients that exhibit impaired mood and cognition improve with liothyronine (L-T3), but the underlying mechanisms remain unknown. Here we show that the T3-indicator mouse carrying the Thr92Ala-DIO2 polymorphism exhibits a hippocampal-specific reduction in T3 activation and signaling that limits the effectiveness of L-T4 therapy. To understand the L-T3 effect, we used a compartmentalized microfluid device and identified a novel neuronal pathway of T3 transport and action that involves axonal T3 uptake into clathrin-dependent, endosomal/non-degradative lysosomes (NDLs). NDLs-containing T3 are retrogradely transported via microtubules, delivering relatively large amounts of T3 to the cell nucleus, doubling the expression of the T3-responsive reporter gene. The NDLs also contain the monocarboxylate transporter 8 (Mct8) and the type 3 deiodinase (Dio3), which transports and inactivates T3, respectively. Notwithstanding, T3 gets away from degradation because D3 active center is in the cytosol. These findings provide (i) a basis for the variable effectiveness of L-T4 therapy, (ii) a pathway for L-T3 to reach neurons, and (iii) resolve the paradox of T3 signaling in the brain amid high D3 activity.

neuroscience↗