Expression Patterns of Hoxb Genes in the Xenopus Embryo Suggest Roles in Anteroposterior Specification of the Hindbrain and in Dorsoventral Patterning of the Mesoderm

Godsave, Susan F.; Dekker, E. J.; Holling, Tjadine M.; Pannese, Maria; Boncinelli, Edoardo; Durston, Antony J.

doi:10.1006/dbio.1994.1330

Cited by 87 publications

(69 citation statements)

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“…We found that the expression pattern of Hox genes in both intermediate and paraxial mesodermal tissues is similar at least regarding the genes examined (except for Hoxb5, which is expressed in the LPM and IM but not in PAM). In Xenopus embryo at the tailbud stage, Hoxb4, Hoxb5, and Hoxb7 are expressed in the pronephric duct; the expression of Hoxb4 in the pronephric duct is visible at an A-P level similar to its somitic expression (Godsave et al, 1994). This phenomenon suggests that both mesodermal tissues are under the same A-P patterning control and are probably specified as two distinguished mesoderm tissues from the same developmental field.…”

Section: Discussionmentioning

confidence: 92%

Comparative spatiotemporal analysis of Hox gene expression in early stages of intermediate mesoderm formation

Barak

Noon

Reshef

2012

Developmental Dynamics

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Background: Hox genes are key players in AP patterning of the vertebrate body plan and are necessary for organogenesis. Several studies provide evidence for the role Hox genes play during kidney development and especially regarding metanephros initiation and formation. However, the role Hox genes play during early stages of kidney development is largely unknown. A recent study in our lab revealed the role Hoxb4 plays in conferring the competence of intermediate mesodermal cells to respond to kidney inductive signals and express early kidney regulators. Results: As a first step in understanding the role Hox genes play in setting the formation of the pronephros morphogenetic field and the expression of early regulators of kidney development, we studied in detail the expression pattern of 10 Hox genes in relation to the 6th somite axial level, the anterior sharp border of the kidney field. Despite the idea of spatial co-linearity as exemplified in the Hox gene expression pattern in late developmental stages, a very dynamic spatio-temporal expression of these genes was found in early stages. Conclusions: Since mesodermal patterning occurs at gastrula stages, the relevance of a ''Hox code'' at early stages is questioned in this study.

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Section: Discussionmentioning

confidence: 92%

Comparative spatiotemporal analysis of Hox gene expression in early stages of intermediate mesoderm formation

Barak

Noon

Reshef

2012

Developmental Dynamics

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“…1). This is the first comparative study of all three genes, although there is data on aspects of the individual genes (Godsave et al, 1994;Kolm and Sive, 1995;Wacker et al, 2004a). All three PG1 Hox genes begin to be expressed during gastrulation, where they are seen in a ring around the blastopore, with a gap on the dorsal side.…”

Section: Resultsmentioning

confidence: 99%

“…These are the earliest of the Hox genes, with expression starting during gastrulation, and they eventually have their anterior boundary in the hindbrain at the level of rhombomeres (r) 3/4 in most vertebrates (Frohman et al, 1990;Frohman and Martin, 1992;Godsave et al, 1994;Kolm and Sive, 1995;Murphy and Hill, 1991;Sundin et al, 1990;Wilkinson et al, 1989). Hoxa1 is also expressed at a later stage in the fore/midbrain (McClintock et al, 2002;Shih et al, 2001).…”

Section: Introductionmentioning

confidence: 99%

Knockdown of the complete Hox paralogous group 1 leads to dramatic hindbrain and neural crest defects

et al. 2005

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The Hox paralogous group 1 (PG1) genes are the first and initially most anterior Hox genes expressed in the embryo. In Xenopus, the three PG1 genes, Hoxa1, Hoxb1 and Hoxd1, are expressed in a widely overlapping domain, which includes the region of the future hindbrain and its associated neural crest. We used morpholinos to achieve a complete knockdown of PG1 function. When Hoxa1, Hoxb1 and Hoxd1 are knocked down in combination, the hindbrain patterning phenotype is more severe than in the single or double knockdowns, indicating a degree of redundancy for these genes. In the triple PG1 knockdown embryos the hindbrain is reduced and lacks segmentation. The patterning of rhombomeres 2 to 7 is lost, with a concurrent posterior expansion of the rhombomere 1 marker, Gbx2. This effect could be via the downregulation of other Hox genes, as we show that PG1 function is necessary for the hindbrain expression of Hox genes from paralogous groups 2 to 4. Furthermore, in the absence of PG1 function, the cranial neural crest is correctly specified but does not migrate into the pharyngeal arches. Embryos with no active PG1 genes have defects in derivatives of the pharyngeal arches and, most strikingly, the gill cartilages are completely missing. These results show that the complete abrogation of PG1 function in Xenopus has a much wider scope of effect than would be predicted from the single and double PG1 knockouts in other organisms.

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“…We found that 73% of embryos developed with moderate to severe anterior head truncations while 27% appeared phenotypically wild type. Nine morphologically wild-type embryos and 15 presumptive mutants were fixed at early tailbud stage 29/30 and these were subjected to whole-mount in situ hybridization with a probe cocktail to detect otx2, egr2 (formerly krox20) and hoxb9 (Papalopulu et al, 1991;Lamb et al, 1993;Godsave et al, 1994;Blitz and Cho, 1995;Pannese et al, 1995). Mutant embryos show loss of the anterior portion of the otx2 expression domain without effects on more posterior neural expression ( Fig.…”

Section: Efficient Crispr/cas9 Mutagenesis In Pgc Transplantsmentioning

confidence: 99%

Leapfrogging: primordial germ cell transplantation permits recovery of CRISPR/Cas9-induced mutations in essential genes

2016

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CRISPR/Cas9 genome editing is revolutionizing genetic loss-offunction analysis but technical limitations remain that slow progress when creating mutant lines. First, in conventional genetic breeding schemes, mosaic founder animals carrying mutant alleles are outcrossed to produce F1 heterozygotes. Phenotypic analysis occurs in the F2 generation following F1 intercrosses. Thus, mutant analyses will require multi-generational studies. Second, when targeting essential genes, efficient mutagenesis of founders is often lethal, preventing the acquisition of mature animals. Reducing mutagenesis levels may improve founder survival, but results in lower, more variable rates of germline transmission. Therefore, an efficient approach to study lethal mutations would be useful. To overcome these shortfalls, we introduce 'leapfrogging', a method combining efficient CRISPR mutagenesis with transplantation of mutated primordial germ cells into a wild-type host. Tested using Xenopus tropicalis, we show that founders containing transplants transmit mutant alleles with high efficiency. F1 offspring from intercrosses between F0 animals that carry embryonic lethal alleles recapitulate loss-of-function phenotypes, circumventing an entire generation of breeding. We anticipate that leapfrogging will be transferable to other species.

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Expression Patterns of Hoxb Genes in the Xenopus Embryo Suggest Roles in Anteroposterior Specification of the Hindbrain and in Dorsoventral Patterning of the Mesoderm

Cited by 87 publications

References 0 publications

Comparative spatiotemporal analysis of Hox gene expression in early stages of intermediate mesoderm formation

Comparative spatiotemporal analysis of Hox gene expression in early stages of intermediate mesoderm formation

Knockdown of the complete Hox paralogous group 1 leads to dramatic hindbrain and neural crest defects

Leapfrogging: primordial germ cell transplantation permits recovery of CRISPR/Cas9-induced mutations in essential genes

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