The homeodomain factor lbx1 distinguishes two major programs of neuronal differentiation in the dorsal spinal cord.
Dorsal horn neurons in the spinal cord integrate and relay sensory information. Here, we show that the expression of the homeobox gene Lbx1 distinguishes two major neuronal classes generated in the dorsal spinal cord. The Lbx1(-) (class A) and Lbx1(+) (class B) neurons differ in their dependence on roof plate BMP signals for specification and settle in the deep and superficial dorsal horn, respectively. Lbx1 misexpression blocks the differentiation of class A neurons. Conversely, in Lbx1 mutant mice, class B neurons assume the identity of class A neurons. As a consequence, the morphology and neuronal circuitry of the dorsal horn are aberrant. We conclude that Lbx1 distinguishes two major neuronal classes in the dorsal spinal cord and is an important determinant of their distinct differentiation programs.
Müller
Thomas
T
Department of Medical Genetics, Max-Delbrück-Center for Molecular Medicine, 13122 Berlin, Germany.
Brohmann
Henning
H
Pierani
Alessandra
A
Heppenstall
Paul A
PA
Lewin
Gary R
GR
Jessell
Thomas M
TM
Birchmeier
Carmen
C
D000344:Afferent Pathways / Q000002:abnormalities / Q000166:cytology / Q000378:metabolism; D000818:Animals; D030801:Animals, Genetically Modified; D030161:Avian Proteins; D001369:Axons / Q000378:metabolism / Q000648:ultrastructure; D051792:Basic Helix-Loop-Helix Proteins; D019521:Body Patterning / Q000235:genetics*; D002454:Cell Differentiation / Q000235:genetics*; D019070:Cell Lineage / Q000235:genetics*; D002642:Chick Embryo; D004268:DNA-Binding Proteins / Q000235:genetics / Q000378:metabolism; D018507:Gene Expression Regulation, Developmental / Q000235:genetics*; D018398:Homeodomain Proteins / Q000235:genetics* / Q000378:metabolism; D051379:Mice; D008817:Mice, Mutant Strains; D008938:Mitosis / Q000235:genetics; D009124:Muscle Proteins / Q000235:genetics* / Q000378:metabolism; D009154:Mutation / Q000235:genetics; D009421:Nervous System Malformations / Q000235:genetics / Q000378:metabolism / Q000473:pathology; D051763:PAX7 Transcription Factor; D020671:Posterior Horn Cells / Q000002:abnormalities* / Q000166:cytology / Q000378:metabolism; D013126:Spinal Nerve Roots / Q000002:abnormalities / Q000166:cytology / Q000378:metabolism; D013234:Stem Cells / Q000166:cytology / Q000378:metabolism*; D014157:Transcription Factors / Q000235:genetics / Q000378:metabolism
D030161:Avian Proteins; D051792:Basic Helix-Loop-Helix Proteins; D004268:DNA-Binding Proteins; D018398:Homeodomain Proteins; D009124:Muscle Proteins; D051763:PAX7 Transcription Factor; D014157:Transcription Factors; C499317:Ascl1 protein, mouse; C113279:LBX1 protein, Gallus gallus; C491868:Lbx1h protein, mouse; C497322:Pax7 protein, mouse