Restricted patterns of Hoxd10 and Hoxd11 set segmental differences in motoneuron subtype complement in the lumbosacral spinal cord.
During normal vertebrate development, Hoxd10 and Hoxd11 are expressed by differentiating motoneurons in restricted patterns along the rostrocaudal axis of the lumbosacral (LS) spinal cord. To assess the roles of these genes in the attainment of motoneuron subtypes characteristic of LS subdomains, we examined subtype complement after overexpression of Hoxd10 or Hoxd11 in the embryonic chick LS cord and in a Hoxd10 loss-of-function mouse embryo. Data presented here provide evidence that Hoxd10 defines the position of the lateral motor column (LMC) as a whole and, in rostral LS segments, specifically promotes the development of motoneurons of the lateral subdivision of the lateral motor column (LMCl). In contrast, Hoxd11 appears to impart a caudal and medial LMC (LMCm) identity to some motoneurons and molecular profiles suggestive of a suppression of LMC development in others. We also provide evidence that Hoxd11 suppresses the expression of Hoxd10 and the retinoic acid synthetic enzyme, retinaldehyde dehydrogenase 2 (RALDH2). In a normal chick embryo, Hoxd10 and RALDH2 are expressed throughout the LS region at early stages of motoneuron differentiation but their levels decline in Hoxd11-expressing caudal LS segments that ultimately contain few LMCl motoneurons. We hypothesize that one of the roles played by Hoxd11 is to modulate Hoxd10 and local retinoic acid levels and thus, perhaps define the caudal boundaries of the LMC and its subtype complement.
Misra
Mala
M
Department of Neurobiology and Center for Neuroscience, University of Pittsburgh School of Medicine, 3500 Terrace Street, Pittsburgh, PA 15261, USA.
Shah
Veeral
V
Carpenter
Ellen
E
McCaffery
Peter
P
Lance-Jones
Cynthia
C
D000818:Animals; D019521:Body Patterning / Q000502:physiology*; D002454:Cell Differentiation; D002642:Chick Embryo; D015536:Down-Regulation; D004622:Embryo, Mammalian / Q000378:metabolism; D018398:Homeodomain Proteins / Q000235:genetics / Q000378:metabolism*; D007150:Immunohistochemistry; D008159:Lumbar Vertebrae / Q000196:embryology; D051379:Mice; D009046:Motor Neurons / Q000166:cytology / Q000378:metabolism*; D012447:Sacrum / Q000196:embryology; D013116:Spinal Cord / Q000166:cytology / Q000196:embryology* / Q000378:metabolism; D014157:Transcription Factors / Q000235:genetics / Q000378:metabolism*; D014162:Transfection
D018398:Homeodomain Proteins; C490944:Hoxd10 protein, mouse; D014157:Transcription Factors