GAD isoforms exhibit distinct spatiotemporal expression patterns in the developing mouse lens: Correlation with Dlx2 and Dlx5

  title={GAD isoforms exhibit distinct spatiotemporal expression patterns in the developing mouse lens: Correlation with Dlx2 and Dlx5},
  author={Andrea Kwakowsky and Marija Schwirtlich and Qi Zhang and David D. Eisenstat and Ferenc Erd{\'e}lyi and M{\'a}ria Baranyi and Zoya Katarova and G{\'a}bor Szab{\'o}},
  journal={Developmental Dynamics},
Gamma‐aminobutyric acid (GABA), the major inhibitory neurotransmitter of the adult nervous system and its biosynthetic enzyme glutamic acid decarboxylase (GAD) are abundantly expressed in the embryonic nervous system and are involved in the modulation of cell proliferation, migration, and differentiation. Here we describe for the first time the expression of GABA and embryonic and adult GAD isoforms in the developing mouse lens. We show that the GAD isoforms are sequentially induced with… 

GABA neurotransmitter signaling in the developing mouse lens: Dynamic regulation of components and functionality

The data suggest that GABA synthesized locally by GAD, acts through GABA receptors by modulating the intracellular calcium levels, and this work shows that the developing lens expresses also components of GABA signaling downstream of GAD.

The spatiotemporal segregation of GAD forms defines distinct GABA signaling functions in the developing mouse olfactory system and provides novel insights into the origin and migration of GnRH neurons

It is demonstrated that GAD67 and its embryonic splice variant embryonic GAD (EGAD) concomitant with GnRH are dynamically regulated during GnRH neuronal migration in vivo and in two immortalized cell lines representing migratory (GN11) and postmigratory (GT1–7) stage GnRH neurons, respectively.

GABAergic Interneuron Differentiation in the Basal Forebrain Is Mediated through Direct Regulation of Glutamic Acid Decarboxylase Isoforms by Dlx Homeobox Transcription Factors

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Expression of GAD67 and Dlx5 in the taste buds of mice genetically lacking Mash1.

The results suggest that Mash1 is required for the expression of GAD67 and Dlx5 in taste bud cells.

KCC2 expression supersedes NKCC1 in mature fiber cells in mouse and rabbit lenses

The present findings provide further evidence that this fundamental neuronal regulation is extensively conserved in lens and identify additional parallels in the morphogenetic programs that underlie lens fiber cell and neuronal differentiation and contribute to the development of visual acuity.

PTBP-dependent PSD-95 and CamKIIα alternative splicing in the lens

Findings of this dendritic spine scaffold protein PSD-95 and conservation of its key mode of molecular regulation in the lens provides further evidence that key aspects of the neuron morphogenetic program are shared with the lens.

NMDA Glutamate Receptor NR1, NR2A and NR2B Expression and NR2B Tyr-1472 Phosphorylation in the Lens

It is demonstrated that REST-regulated NMDAR NR1, NR2A, and NR2B are also expressed in lenses and localize predominantly in fiber cell membranes, consistent with REST transcription factors, as well as miR-124 and other REST gene targets identified in the lens.

Lens Biology is a Dimension of Neurobiology

The extent and detail of internally consistent parallels with neuron biology now catalogued in their second native cell type in the lens provide a detailed model of interdependent neuron gene expression in lens development and non-neuronal role in vision.

The regulation of glutamic acid decarboxylases in GABA neurotransmission in the brain.

This review focuses on the recent advances in understanding the structure of GAD, its transcriptional regulation and post-transcriptional modifications in the central nervous system and may provide insights into the pathological mechanisms underlying neurological diseases that are associated with GAD dysfunction.



Dynamic expression of a glutamate decarboxylase gene in multiple non-neural tissues during mouse development

Additional structures outside of the central nervous system that express Gad1 are defined, indicating those structures that may require its function for normal development and a wider role for GABA signaling in development than was previously appreciated.

Domain‐restricted expression of two glutamic acid decarboxylase genes in midgestation mouse embryos

The authors studied the cellular distribution of two GAD isoforms in midgestation mouse embryos by in situ hybridization histochemistry and found that GAD65 and GAD67 mRNAs are localized in overlapping cellular domains of the embryonic CNS that later develop into regions with a strong GABAergic contribution.

Prox1 expression patterns in the developing and adult murine brain

A detailed analysis of Prox1 mRNA and protein expression during prenatal and postnatal murine brain development and adulthood suggests that prox1 activity is differentially required during brainDevelopment and adulthood.

Transient expression of glutamate decarboxylase and γ‐amino butyric acid in embryonic lens fibers of the rat

It is speculated on the basis of possible common gene regulatory elements for glutamate and ornithine decarboxylases and the involvement of these enzymes with polyamine synthesis, that the transient expression of GAD67 may be connected to nuclear and/or DNA breakdown during lens fiber cell differentiation.

Dlx1 and Dlx2 function is necessary for terminal differentiation and survival of late-born retinal ganglion cells in the developing mouse retina

A model whereby early-born RGCs are Dlx1 and Dl x2 independent, but DlX function is necessary for terminal differentiation of late- born RGC progenitors is proposed.

Dlx1, Dlx2, Pax6, Brn3b, and Chx10 homeobox gene expression defines the retinal ganglion and inner nuclear layers of the developing and adult mouse retina

The correlation ofDLX2 with GABA expression in the mouse retina closely mirrors the relationship of DLX2 to GABAergic neuronal differentiation in the embryonic forebrain, including neocortex, olfactory bulb and hippocampus, signifying a conservation of function of Dlx genes in the developing central nervous system.

Expression of the genes GAD67 and Distal‐less‐4 in the forebrain of Xenopus laevis confirms a common pattern in tetrapods

The close correlation in the expression of both genes in rostral forebrain regions supported the notion that Dll/Dlx are among the genes involved in the acquisition of the GABAergic phenotype.