科研之友
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摘要
The Pcdh-gamma 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 del motor neurons (MNs), do not undergo excessive apoptosis in Pcdh-y" del null mutants, which die shortly after birth. However, as we show here, mutants exhibit severely disorganized la proprioceptive afferent terminals in the ventral horn. In contrast to the fine net-like pattern observed in wild-type mice, central la terminals in Pcdh-y mutants appear clumped, and fill the space between individual MNs; quantitative analysis shows a 2.5fold increase in the area of terminals. Concomitant with this, there is a 70% loss of the collaterals that la afferents extend to ventral interneurons (vINs), many of which undergo apoptosis in the mutants. The la afferent phenotype is ameliorated, though not entirely rescued, when apoptosis is blocked in Pcdh-y null mice by introduction of a Bax null allele. This indicates that loss of vINs, which act as collateral la afferent targets, contributes to the disorganization of terminals on motor pools. Restricted mutation of the Pcdh-y cluster using conditional mutants and multiple Cre transgenic lines (Wni-I-Cre for sensory neurons; Pax2-Cre for vINs; Hb9-Cre for MNs) also revealed a direct requirement for the y-Pcdhs in la neurons and vINs, but not in MNs themselves. Together, these genetic manipulations indicate that the y-Pcdhs are required for the formation of the la afferent circuit in two ways: First, they control the survival of vINs that act as collateral la targets; and second, they provide a homophilic molecular cue between la afferents and target vINs.
- 出版日期2011
