RESUMEN
Little is known of transcriptional mechanisms underlying the development of the trigeminal (V) principal sensory nucleus (PrV), the brainstem nucleus responsible for the development of the whisker-to-barrel cortex pathway. Lmx1b, a LIM homeodomain transcription factor, is expressed in embryonic PrV. In Lmx1b knockout ((-)(/)(-)) mice, V primary afferent projections to PrV are normal, albeit reduced in number, whereas the PrV-thalamic lemniscal pathway is sparse and develops late. Excess cell death occurs in the embryonic Lmx1b(-)(/)(-) PrV, but not in Lmx1b/Bax double null mutants. Expression of Drg11, a downstream transcription factor essential for PrV development and pattern formation, is abolished in PrV, but not in the V ganglion. Consequently, whisker patterns fail to develop in PrV by birth. Rescued PrV cells in Lmx1b/Bax double (-)(/)(-)s failed to rescue whisker-related PrV pattern formation. Thus, Lmx1b and Drg11 may act in the same genetic signaling pathway that is essential for PrV pattern formation.
Asunto(s)
Tipificación del Cuerpo/genética , Proteínas de Homeodominio/fisiología , Factores de Transcripción/fisiología , Núcleos del Trigémino/embriología , Vibrisas/inervación , Vías Aferentes/fisiología , Animales , Animales Recién Nacidos , Muerte Celular/genética , Proteínas de Homeodominio/genética , Proteínas con Homeodominio LIM , Ratones , Ratones Endogámicos C57BL , Ratones Noqueados , Proteínas del Tejido Nervioso/deficiencia , Proteínas del Tejido Nervioso/genética , Tálamo/citología , Tálamo/embriología , Factores de Transcripción/deficiencia , Factores de Transcripción/genética , Ganglio del Trigémino/citología , Ganglio del Trigémino/embriología , Núcleos del Trigémino/citología , Núcleos del Trigémino/metabolismo , Proteína X Asociada a bcl-2/deficienciaRESUMEN
The dorsal horn of the spinal cord consists of distinct laminae that serve as a pivotal region for relaying a variety of somatosensory signals such as temperature, pain, and touch. The molecular mechanisms underlying the development of the dorsal horn are poorly understood. To define a molecular map of the dorsal horn circuit, we have profiled dorsal horn-enriched (DHE) gene expression in dorsal spinal cords on embryonic day 15.5 (E15.5) by genome-wide microarray and smart subtractive screening based on polymerase chain reaction (PCR). High-throughput in situ hybridization (ISH) was carried out to validate the expression of 379 genes in the developing dorsal spinal cord. A total of 113 DHE genes were identified, of which 59% show lamina-specific expression patterns. Most lamina-specific genes were expressed across at least two laminae, however. About 32% of all DHE genes are transcription factors, which represent the largest percentage of the group of all DHE functional classifications. Importantly, several individual lamina-specific transcription factors such c-Maf, Rora, and Satb1 are identified for the first time. Epistasis studies revealed several putative effectors of known DHE transcription factors such as Drg11, Tlx3(Rnx), and Lmx1b. These effector genes, including Grp, Trpc3, Pcp4, and Enc1, have been implicated in synaptic transmission, calcium homeostasis, and structural function and thus may have similar roles in the dorsal horn. The identification of a large number of DHE genes, especially those that are lamina specific, lays a foundation for future studies on the molecular machinery that controls the development of the dorsal horn and on functional differences of these distinct laminae in the dorsal spinal cord.