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A differential developmental pattern of spinal interneuron apoptosis during synaptogenesis: insights from genetic analyses of the protocadherin-gamma gene cluster
Journal article   Open access   Peer reviewed

A differential developmental pattern of spinal interneuron apoptosis during synaptogenesis: insights from genetic analyses of the protocadherin-gamma gene cluster

Tuhina Prasad, Paul A Gray, Joshua A Weiner and Xiaozhong Wang
Development (Cambridge), Vol.135(24), pp.4153-4164
12/2008
DOI: 10.1242/dev.026807
PMCID: PMC2755264
PMID: 19029045
url
https://doi.org/10.1242/dev.026807View
Published (Version of record) Open Access

Abstract

Although the role of developmental apoptosis in shaping the complement and connectivity of sensory and motoneurons is well documented, the extent to which cell death affects the 13 cardinal classes of spinal interneurons is unclear. Using a series of genetic manipulations in vivo, we demonstrate for the first time a differential pattern of developmental apoptosis in molecularly identified spinal interneuron populations, and implicate the adhesion molecule family encoded by the 22-member protocadherin-gamma (Pcdh-gamma) gene cluster in its control. In constitutive Pcdh-gamma null mouse embryos, many interneuron populations undergo increased apoptosis, but to differing extents: for example, over 80% of En1-positive V1 neurons are lost, whereas only 30% of Chx10-positive V2a neurons are lost and there is no reduction in the number of V1-derived Renshaw cells. We show that this represents an exacerbation of a normal, underlying developmental pattern: the extent of each population's decrease in Pcdh-gamma mutants is precisely commensurate both with the extent of its loss during normal embryogenesis and with the extent of its increase in Bax(-/-) mice, in which apoptosis is genetically blocked. Interneuron apoptosis begins during the first wave of synaptogenesisis in the spinal cord, occurring first among ventral populations (primarily between E14 and E17), and only later among dorsal populations (primarily after P0). Utilizing a new, conditional Pcdh-gamma mutant allele, we show that the gamma-Pcdhs can promote survival non-cell-autonomously: mutant neurons can survive if they are surrounded by normal neurons, and normal neurons can undergo apoptosis if they are surrounded by mutant neurons.
 Mutation Interneurons - physiology Multigene Family Apoptosis - genetics DNA Primers - genetics Neurogenesis - genetics Gene Expression Regulation, Developmental Mice, Mutant Strains Base Sequence Interneurons - cytology Spinal Cord - cytology Cadherins - genetics Mice, Transgenic Cadherins - physiology Body Patterning - physiology Mice, Knockout Spinal Cord - embryology Animals Neurogenesis - physiology Alleles Mice Apoptosis - physiology Body Patterning - genetics Cadherins - deficiency Cell Movement

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