title: Loss of Growth arrest specific gene 6 (Gas6) results in altered GnRH neuron migration, delayed vaginal opening and sexual maturation in mice.
abstract: Prior work has shown the importance of TAM (Tyro3, Axl, Mer) receptor tyrosine kinases in GnRH neuronal development and reproductive function. It is unclear if TAM receptor actions are dependent on ligand activation for their functional effects; thus, we characterized reproductive phenotype of ligand Growth arrest specific gene (Gas6) null mice. Gas6 null mice showed delayed vaginal opening and delayed first estrus. Animals eventually attained normal estrous cycles as adults. The GnRH neuronal population was significantly decreased in Gas6 null adults and embryos, but the final positioning of cell bodies in the hypothalamus was normal. Vaginal tissue showed up-regulation of TAM receptor mRNAs in the absence of the ligand. These data confirm that Gas6 plays a role in early GnRH neuronal development and during vaginal opening. The phenotype of Gas6 KO mice suggests that TAMs function in a ligand-dependent and independent manner to control GnRH neuron development to modulate normal reproductive function.
authors: Departments of Medicine, University of Colorado, School of Medicine, Aurora, CO 80045, USA.
authors: Smita
authors: S
authors: Salian-Mehta
authors: Departments of Medicine, University of Colorado, School of Medicine, Aurora, CO 80045, USA.
authors: Mei
authors: M
authors: Xu
authors: Departments of Medicine, University of Colorado, School of Medicine, Aurora, CO 80045, USA.
authors: Angela
authors: A
authors: Pierce
authors: Departments of Medicine, University of Colorado, School of Medicine, Aurora, CO 80045, USA.
authors: Brian
authors: B
authors: Bliesner
authors: Department of Biomedical Sciences, Colorado State University, Fort Collins, CO 80523, USA.
authors: Stuart
authors: S
authors: Tobet
authors: Departments of Medicine, University of Colorado, School of Medicine, Aurora, CO 80045, USA; Research Service VAMC, Denver, CO 80220, USA. Electronic address: margaret.wierman@ucdenver.edu.
authors: Margaret E
authors: ME
authors: Wierman
mesh_terms: D000818:Animals; D002465:Cell Movement / Q000235:genetics; D005260:Female; D007150:Immunohistochemistry; D036341:Intercellular Signaling Peptides and Proteins / Q000235:genetics* / Q000378:metabolism; D051379:Mice; D018345:Mice, Knockout; D009474:Neurons / Q000166:cytology* / Q000502:physiology*; D060888:Real-Time Polymerase Chain Reaction; D012741:Sexual Maturation / Q000235:genetics*; D014621:Vagina / Q000254:growth & development*; D000099255:Growth Arrest-Specific Protein 6
chemical_list: D036341:Intercellular Signaling Peptides and Proteins; D000099255:Growth Arrest-Specific Protein 6
keywords: Gas6; GnRH neurons; TAM family