Evolutionarily conserved function of Gbx2 in anterior hindbrain development

Burroughs‐Garcia, Jessica; Sittaramane, Vinoth; Chandrasekhar, Anand; Waters, Samuel T.

doi:10.1002/dvdy.22589

Cited by 14 publications

(19 citation statements)

References 52 publications

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“…Consistent with this, careful analysis of gbx1 morphant zebrafish identified a subtle and transient defect in the anterior hindbrain development (Rhinn et al, 2009). Two other reports (Burroughs-Garcia et al, 2011; Kikuta et al, 2003) described dramatic defects in the development of the anterior hindbrain in gbx2 morphant zebrafish, suggestive of a strong independent requirement for gbx2 akin to the situation in the mouse. By making genetic null mutations in both genes we have now demonstrated that gbx2 expression compensates for the lack of gbx1 in the Zebrafish as predicted by Rhinn et al (Rhinn et al, 2009; Rhinn et al, 2003).…”

Section: Discussionmentioning

confidence: 85%

Cerebellar development in the absence of Gbx function in zebrafish

Kemp

Moens

2014

Developmental Biology

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The midbrain-hindbrain boundary (MHB) is a well-known organizing center during vertebrate brain development. The MHB forms at the expression boundary of Otx2 and Gbx2, mutually repressive homeodomain transcription factors expressed in the midbrain/forebrain and anterior hindbrain, respectively. The genetic hierarchy of gene expression at the MHB is complex, involving multiple positive and negative feedback loops that result in the establishment of non-overlapping domains of Wnt1 and Fgf8 on either side of the boundary and the consequent specification of the cerebellum. The cerebellum derives from the dorsal part of the anterior-most hindbrain segment, rhombomere 1 (r1), which undergoes a distinctive morphogenesis to give rise to the cerebellar primordium within which the various cerebellar neuron types are specified. Previous studies in the mouse have shown that Gbx2 is essential for cerebellar development. Using zebrafish mutants we show here that in the zebrafish gbx1 and gbx2 are required redundantly for morphogenesis of the cerebellar primordium and subsequent cerebellar differentiation, but that this requirement is alleviated by knocking down Otx. Expression of fgf8, wnt1 and the entire MHB genetic program is progressively lost in gbx1-;gbx2- double mutants but is rescued by Otx knock-down. This rescue of the MHB genetic program depends on rescued Fgf signaling, however the rescue of cerebellar primordium morphogenesis is independent of both Gbx and Fgf. Based on our findings we propose a revised model for the role of Gbx in cerebellar development.

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Section: Discussionmentioning

confidence: 85%

Cerebellar development in the absence of Gbx function in zebrafish

Kemp

Moens

2014

Developmental Biology

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“…Previous studies showed that in mice, Gbx2 is involved in early specification of the midbrain-hindbrain boundary (MHB) organizer, a signaling center that will pattern the anterior hindbrain rhombomeres (Wassarman et al, 1997; Waters & Lewandoski, 2006; for review: Rhinn & Brand, 2001; Simeone, 2000). In zebrafish it was shown that Gbx1 acts during early positioning of the MHB, whereas Gbx2 functions at later stages, once the MHB is established (Rhinn et al, 2003; Rhinn et al, 2009; Burroughs-Garcia et al, 2011). In mice, Gbx1 is not expressed at the MHB as is the case during early zebrafish development.…”

Section: Resultsmentioning

confidence: 99%

The homeodomain factorGbx1is required for locomotion and cell specification in the dorsal spinal cord

Méziane

Fraulob

Riet

et al. 2013

PeerJ

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Dorsal horn neurons in the spinal cord integrate and relay sensory information to higher brain centers. These neurons are organized in specific laminae and different transcription factors are involved in their specification. The murine homeodomain Gbx1 protein is expressed in the mantle zone of the spinal cord at E12.5-13.5, correlating with the appearance of a discernable dorsal horn around E14 and eventually defining a narrow layer in the dorsal horn around perinatal stages. At postnatal stages, Gbx1 identifies a specific subpopulation of GABAergic neurons in the dorsal spinal cord. We have generated a loss of function mutation for Gbx1 and analyzed its consequences during spinal cord development. Gbx1−/− mice are viable and can reproduce as homozygous null mutants. However, the adult mutant mice display an altered gait during forward movement that specifically affects the hindlimbs. This abnormal gait was evaluated by a series of behavioral tests, indicating that locomotion is impaired, but not muscle strength or motor coordination. Molecular analysis showed that the development of the dorsal horn is not profoundly affected in Gbx1−/− mutant mice. However, analysis of terminal neuronal differentiation revealed that the proportion of GABAergic inhibitory interneurons in the superficial dorsal horn is diminished. Our study unveiled a role for Gbx1 in specifying a subset of GABAergic neurons in the dorsal horn of the spinal cord involved in the control of posterior limb movement.

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“…In hindbrain Cdx1 also transiently represses Kreisler (Mafb) restricting its expression anterior of the r6/r7 boundary [54]. Gbx2 is a Wnt-target that plays an important role in the formation of the mid-hindbrain border and also specifies the anterior hindbrain [46]. Besides its role in axial elongation and axial mesoderm specification, the Wnt target gene Grsf1 is also involved in mid/hindbrain development, where it is necessary for maintaining Fgf8 and Gbx2 expression [55].…”

Section: Wecmentioning

confidence: 98%

“…Besides Hox genes, the Gbx and Otx gene families have important roles in body segmentation throughout the animal kingdom [45]. Gbx2 particularly determines the mid-hindbrain boundary in mice [46].…”

Section: Cellular Proliferation Migration and Differentiationmentioning

confidence: 99%