RESUMEN
We used the cerebellum as a model to study the morphogenetic and cellular processes underlying the formation of elaborate brain structures from a simple neural tube, using an inducible genetic fate mapping approach in mouse. We demonstrate how a 90 degrees rotation between embryonic days 9 and 12 converts the rostral-caudal axis of dorsal rhombomere 1 into the medial-lateral axis of the wing-like bilateral cerebellar primordium. With the appropriate use of promoters, we marked specific medial-lateral domains of the cerebellar primordium and derived a positional fate map of the murine cerebellum. We show that the adult medial cerebellum is produced by expansion, rather than fusion, of the thin medial primordium. Furthermore, ventricular-derived cells maintain their original medial-lateral coordinates into the adult, whereas rhombic lip-derived granule cells undergo lateral to medial posterior transverse migrations during foliation. Thus, we show that progressive changes in the axes of the cerebellum underlie its genesis.
Asunto(s)
Diferenciación Celular/genética , Linaje de la Célula/genética , Movimiento Celular/genética , Cerebelo/embriología , Morfogénesis/fisiología , Células Madre/metabolismo , Animales , Tipificación del Cuerpo/genética , Cerebelo/citología , Cerebelo/metabolismo , Quimera , Femenino , Regulación del Desarrollo de la Expresión Génica/genética , Marcadores Genéticos , Proteínas de Homeodominio/genética , Integrasas/genética , Masculino , Ratones , Ratones Endogámicos C57BL , Ratones Transgénicos , Proteínas del Tejido Nervioso/genética , Neuronas/citología , Neuronas/metabolismo , Regiones Promotoras Genéticas/genética , Células Madre/citologíaRESUMEN
Brain structures derived from the mesencephalon (mes) and rhombomere 1 (r1) modulate distinct motor and sensory modalities. The precise origin and cellular behaviors underpinning the cytoarchitectural organization of the mes and r1, however, are unknown. Using a novel inducible genetic fate mapping approach in mouse, we determined the fate and lineage relationships of mes/r1 cells with fine temporal and spatial resolution. We demonstrate that the mes and r1 are neuromeres that along with the isthmic organizer are partitioned along the anterior-posterior axis by lineage restriction boundaries established sequentially between E8.5 and E9.5. Furthermore, a small group of cells originating from the most posterior mes exhibit anterior intracompartmental expansion and contribute throughout the inferior colliculus. Finally, we also uncovered transient and differential genetic lineages of ventral midbrain dopaminergic and ventral hindbrain serotonergic neuronal precursors with respect to Wnt1 and Gli1 expression.
Asunto(s)
Regulación del Desarrollo de la Expresión Génica/genética , Mesencéfalo/embriología , Mesencéfalo/metabolismo , Rombencéfalo/embriología , Rombencéfalo/metabolismo , Animales , Linaje de la Célula/genética , Femenino , Factores de Transcripción de Tipo Kruppel , Masculino , Mesencéfalo/citología , Ratones , Ratones Transgénicos , Neuronas/fisiología , Embarazo , Proteínas Proto-Oncogénicas/biosíntesis , Proteínas Proto-Oncogénicas/genética , Rombencéfalo/citología , Factores de Transcripción/biosíntesis , Factores de Transcripción/genética , Proteínas Wnt , Proteína Wnt1 , Proteína con Dedos de Zinc GLI1RESUMEN
The midbrain/hindbrain (MH) territory containing the mesencephalic and isthmocerebellar primordial is characterized by the expression of several families of regulatory genes including transcription factors (Otx, Gbx, En, and Pax) and signaling molecules (Fgf and Wnt). At earlier stages of avian neural tube, those genes present a dynamic expression pattern and only at HH18-20 onwards, when the mesencephalic/metencephalic constriction is coincident with the Otx2/Gbx2 boundary, their expression domains become more defined. This review summarizes experimental data concerning the genetic mechanisms involved in the specification of the midbrain/hindbrain territory emphasizing the chick/quail chimeric experiments leading to the discovery of a secondary isthmic organizer. Otx2 and Gbx2 co-regulation could determine the precise location of the MH boundary and involved in the inductive events characteristic of the isthmic organizer center.