Homeodomain transcription factors in the development of subsets of hindbrain reticulospinal neurons

Cepeda‐Nieto, Ana Cecilia; Pfaff, Samuel L.; Varela‐Echavarría, Alfredo

doi:10.1016/j.mcn.2004.06.016

Cited by 47 publications

(42 citation statements)

References 43 publications

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“…For all experiments, we used Chx10-EGFP transgenic mice, which express GFP in the hindbrain, spinal cord, and other areas of the CNS in which Chx10-positive cells have been described to be expressed (Rowan and Cepko, 2004;Cepeda-Nieto et al, 2005;Al-Mosawie et al, 2007;Lundfald et al, 2007;Crone et al, 2008) (Allen Institute for Brain Science, 2009; available from: http:// developingmouse.brain-map.org/). Here, we focus on the lumbar spinal cord (L2-L5) in which the CPG controlling hindlimb locomotion is localized (Kiehn and Kjaerulff 1998).…”

Section: Chx10-gfp Distribution In the Spinal Cordmentioning

confidence: 99%

Firing and Cellular Properties of V2a Interneurons in the Rodent Spinal Cord

Dougherty¹,

Kiehn²

2010

J. Neurosci.

123

125

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Section: Chx10-gfp Distribution In the Spinal Cordmentioning

confidence: 99%

Firing and Cellular Properties of V2a Interneurons in the Rodent Spinal Cord

Dougherty¹,

Kiehn²

2010

J. Neurosci.

123

125

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“…Furthermore, 10/30 validated predictions contained at least one PAX family motif (enrichment of 1.8 as compared with random genomic sequences with similar length and GC-content, P-value = 0.05, Fisher's exact test). Finally, a number of sequences share in common an LHX3 motif that binds a LIM domain TF with a role in neuronal specification (Cepeda-Nieto et al 2005;Gadd et al 2011), resulting in an enrichment of 4.6 (P-value = 0.0002, Fisher's exact test). HB25 and HB51 both contain an LHX3 TFBS and share many overlapping domains of reporter expression, including in the Hb and spinal column, which is consistent with endogenous lhx3 expression ( Fig.…”

Section: Genome-wide Predictions Identify Novel Hindbrain Enhancersmentioning

confidence: 99%

Systematic elucidation and in vivo validation of sequences enriched in hindbrain transcriptional control

et al. 2012

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Illuminating the primary sequence encryption of enhancers is central to understanding the regulatory architecture of genomes. We have developed a machine learning approach to decipher motif patterns of hindbrain enhancers and identify 40,000 sequences in the human genome that we predict display regulatory control that includes the hindbrain. Consistent with their roles in hindbrain patterning, MEIS1, NKX6-1, as well as HOX and POU family binding motifs contributed strongly to this enhancer model. Predicted hindbrain enhancers are overrepresented at genes expressed in hindbrain and associated with nervous system development, and primarily reside in the areas of open chromatin. In addition, 77 (0.2%) of these predictions are identified as hindbrain enhancers on the VISTA Enhancer Browser, and 26,000 (60%) overlap enhancer marks (H3K4me1 or H3K27ac). To validate these putative hindbrain enhancers, we selected 55 elements distributed throughout our predictions and six low scoring controls for evaluation in a zebrafish transgenic assay. When assayed in mosaic transgenic embryos, 51/55 elements directed expression in the central nervous system. Furthermore, 30/34 (88%) predicted enhancers analyzed in stable zebrafish transgenic lines directed expression in the larval zebrafish hindbrain. Subsequent analysis of sequence fragments selected based upon motif clustering further confirmed the critical role of the motifs contributing to the classifier. Our results demonstrate the existence of a primary sequence code characteristic to hindbrain enhancers. This code can be accurately extracted using machine-learning approaches and applied successfully for de novo identification of hindbrain enhancers. This study represents a critical step toward the dissection of regulatory control in specific neuronal subtypes.[Supplemental material is available for this article.]In metazoans, precise spatiotemporal patterns of gene expression are modulated by the exquisite contributions of transcriptional regulatory sequences. These include enhancers that activate transcription in a manner frequently observed to be independent of distance, position, and orientation with respect to the promoter of their target genes (Banerji et al. 1981). Empirically validated enhancers are typically a few hundred base pairs long and comprise binding sites for multiple transcription factors (TFs). In turn, TFs bound to these sequences also interact with common co-activators, communicating with the basal transcription machinery assembled at the promoter, and increasing the rate of transcription (Bulger and Groudine 2011). Identifying the combinatorial protein-DNA and protein-protein interactions that determine spatial and temporal enhancer function is crucial to understanding how distinct cellular and developmental programs are established.The systematic discovery of enhancers has proven challenging, since they are often located at great genomic distances from the genes they regulate (Lettice et al. 2003). The classical approach to enhancer identification invo...

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“…Further support for dIN involvement in rhythm generation comes from the finding that reticulospinal dIN activity precedes that of other locomotor neurons during the swimming cycle [52•]. In this context it is worth noting that the genetic program that defines neuronal subtypes such as V2a INs in the developing spinal cord also operates in the hindbrain [57] and that mice lacking V2a INs exhibit clear deficits in brainstem-initiated fictive locomotion [39••]. …”

Section: Motor Circuits In the Spinal Cord: Lessons From The “V” Intementioning

confidence: 99%

From circuits to behaviour: motor networks in vertebrates

García‐Campmany

Stam

Goulding

2010

Current Opinion in Neurobiology

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Neural networks in the hindbrain and spinal cord generate the simple patterns of motor activity that are necessary for breathing and locomotion. These networks function autonomously, producing simple yet flexible rhythmic motor behaviours that are highly responsive to sensory inputs and central control. This review highlights recent advances in our understanding of the genetic programs that control the assembly and functioning of the hindbrain and spinal circuits that are responsible for respiration and locomotion. In addition, we highlight the influence that target-derived retrograde signaling and experience-dependent mechanisms have on establishing connectivity, particularly with respect to sensory circuits in the spinal cord.

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Homeodomain transcription factors in the development of subsets of hindbrain reticulospinal neurons

Cited by 47 publications

References 43 publications

Firing and Cellular Properties of V2a Interneurons in the Rodent Spinal Cord

Firing and Cellular Properties of V2a Interneurons in the Rodent Spinal Cord

Systematic elucidation and in vivo validation of sequences enriched in hindbrain transcriptional control

From circuits to behaviour: motor networks in vertebrates

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