Journal article
Direct and Indirect Regulation of Spinal Cord Ia Afferent Terminal Formation by the γ-Protocadherins
Frontiers in molecular neuroscience, Vol.4, pp.54-54
2011
DOI: 10.3389/fnmol.2011.00054
PMCID: PMC3250626
PMID: 22275881
Abstract
The
Pcdh-γ
gene cluster encodes 22 protocadherin adhesion molecules that interact as homophilic multimers and critically regulate synaptogenesis and apoptosis of interneurons in the developing spinal cord. Unlike interneurons, the two primary components of the monosynaptic stretch reflex circuit, dorsal root ganglion sensory neurons and ventral motor neurons (MNs), do not undergo excessive apoptosis in
Pcdh-γ
del/del
null mutants, which die shortly after birth. However, as we show here, mutants exhibit severely disorganized Ia proprioceptive afferent terminals in the ventral horn. In contrast to the fine net-like pattern observed in wild-type mice, central Ia terminals in
Pcdh-γ
mutants appear clumped, and fill the space between individual MNs; quantitative analysis shows a ~2.5-fold increase in the area of terminals. Concomitant with this, there is a 70% loss of the collaterals that Ia afferents extend to ventral interneurons (vINs), many of which undergo apoptosis in the mutants. The Ia afferent phenotype is ameliorated, though not entirely rescued, when apoptosis is blocked in
Pcdh-γ
null mice by introduction of a
Bax
null allele. This indicates that loss of vINs, which act as collateral Ia afferent targets, contributes to the disorganization of terminals on motor pools. Restricted mutation of the
Pcdh-γ
cluster using conditional mutants and multiple Cre transgenic lines (
Wnt1-Cre
for sensory neurons;
Pax2-Cre
for vINs;
Hb9-Cre
for MNs) also revealed a direct requirement for the γ-Pcdhs in Ia neurons and vINs, but not in MNs themselves. Together, these genetic manipulations indicate that the γ-Pcdhs are required for the formation of the Ia afferent circuit in two ways: First, they control the survival of vINs that act as collateral Ia targets; and second, they provide a homophilic molecular cue between Ia afferents and target vINs.
Details
- Title: Subtitle
- Direct and Indirect Regulation of Spinal Cord Ia Afferent Terminal Formation by the γ-Protocadherins
- Creators
- Tuhina Prasad - Department of Biology, The University of IowaJoshua A Weiner - Department of Biology, The University of Iowa
- Resource Type
- Journal article
- Publication Details
- Frontiers in molecular neuroscience, Vol.4, pp.54-54
- DOI
- 10.3389/fnmol.2011.00054
- PMID
- 22275881
- PMCID
- PMC3250626
- NLM abbreviation
- Front Mol Neurosci
- ISSN
- 1662-5099
- eISSN
- 1662-5099
- Publisher
- Frontiers Research Foundation
- Language
- English
- Date published
- 2011
- Academic Unit
- Liberal Arts and Science Admin; Psychiatry; Iowa Neuroscience Institute; Biology
- Record Identifier
- 9983997972502771
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