Cadherin-7 and cadherin-6B differentially regulate the growth, branching and guidance of cranial motor axons.
Cadherin-7 (Cad7) and cadherin-6B (Cad6B) are expressed in early and late phases of cranial motoneuron development, respectively. Cad7 is expressed by cranial motoneurons soon after they are generated, as well as in the environment through which their axons extend. By contrast, Cad6B is expressed by mature cranial motoneurons. We demonstrate in chick that these cadherins play distinct roles in cranial motor axon morphology, branching and projection. Using in vitro approaches, we show that Cad7 enhances motor axon outgrowth, suppresses the formation of multiple axons and restricts interstitial branching, thus promoting the development of a single unbranched axon characteristic of differentiating motoneurons. Conversely, Cad6B in vitro promotes motor axon branching, a characteristic of mature motoneurons. In vivo gain- and loss-of-function experiments for these cadherins yielded phenotypes consistent with this interpretation. In particular, a loss of cadherin-mediated interactions in vivo led to dysregulation of the cranial motoneuron normal branching programme and caused axon navigation defects. We also demonstrate that Cad6B functions via the phosphatidylinositol 3-kinase pathway. Together, these data show that Cad7 and Cad6B differentially regulate cranial motoneuron growth, branching and axon guidance.
MRC Centre for Developmental Neurobiology, 4th Floor New Hunt's House, Kings College, Guy's Campus, London SE1 1UL, UK.
Sarah H
SH
Barnes
Stephen R
SR
Price
Corinna
C
Wentzel
Sarah C
SC
Guthrie
D000818:Animals; D030161:Avian Proteins / Q000235:genetics / Q000378:metabolism / Q000502:physiology*; D001370:Axonal Transport / Q000235:genetics / Q000502:physiology; D001369:Axons / Q000378:metabolism / Q000502:physiology*; D015820:Cadherins / Q000235:genetics / Q000378:metabolism / Q000502:physiology*; D002454:Cell Differentiation / Q000235:genetics; D049109:Cell Proliferation; D002478:Cells, Cultured; D002642:Chick Embryo; D003391:Cranial Nerves / Q000378:metabolism / Q000502:physiology*; D018507:Gene Expression Regulation, Developmental; D006801:Humans; D051379:Mice; D009046:Motor Neurons / Q000378:metabolism / Q000502:physiology*; D041681:NIH 3T3 Cells; D009434:Neural Pathways / Q000378:metabolism; D055495:Neurogenesis / Q000235:genetics
D030161:Avian Proteins; C094294:Cad7 protein, Gallus gallus; D015820:Cadherins; C094293:cad6B protein, Gallus gallus