A new serine/threonine protein kinase,<i>Omphk1</i>, essential to ventral body wall formation

Hirano, Mariko; Kanazawa, Hiroshi; Furushima, Kaoru; Murata, Takuya; Suda, Yoko; Aizawa, Shinichi

doi:10.1002/dvdy.20823

Cited by 24 publications

(48 citation statements)

References 29 publications

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“…We also performed bioinformatics analysis to determine sequence conservation between these two homologs. The expression patterns we describe are similar to those previously obtained for NUAK1 in wild-type mice embryos using a b Gal fusion protein (Hirano et al, 2006). In the chick, the regionally-restricted expression of NUAK isoforms overlaps.…”

Section: Resultssupporting

confidence: 82%

“…Although these genes are mainly expressed in the neuroectoderm in mouse, it has been reported that NUAK1 mutants exhibit no apparent gross brain defects, but do have ventral body wall defects (Hirano et al, 2006). Mice deficient in both NUAK1 and NUAK2 display exencephaly, facial clefting, and spina bifida, suggesting partially redundant activity for these two genes (Ohmura et al, 2012).…”

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confidence: 99%

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Analysis of NUAK1 and NUAK2 expression during early chick development reveals specific patterns in the developing head

Bekri¹,

Billaud²,

Thélu³

2014

Int. J. Dev. Biol.

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Several human diseases are associated with the NUAK1 and NUAK2 genes. These genes encode kinases, members of the AMPK-related kinases (ARK) gene family. Both NUAK1 and NUAK2 are known targets of the serine threonine kinase LKB1, a tumor suppressor involved in regulating cell polarity. While much is known about their functions in disease, their expression pattern in normal development has not been extensively studied. Here, we present the expression patterns for NUAK1 and NUAK2 in the chick during early-stage embryogenesis, until day 3 (Hamburger and Hamilton stage HH20). Several embryonic structures, in particular the nascent head, showed distinct expression levels. NUAK1 expression was first detected at stage HH6 in the rostral neural folds. It was then expressed (HH7-11) throughout the encephalalon, predominantly in the telencephalon and mesencephalon. NUAK1 expression was also detected in the splanchnic endoderm area at HH8-10, and in the vitellin vein derived from this area, but not in the heart. NUAK2 expression was first detected at stage HH6 in the neural folds. It was then found throughout the encephalon at stage HH20. Particular attention was paid in this study to the dorsal ectoderm at stages HH7 and HH8, where a local deficit or accumulation of NUAK2 mRNA were found to correlate with the direction of curvature of the neural plate. This is the first description of NUAK1 and NUAK2 expression patterns in the chick during early development; it reveals non-identical expression profiles for both genes in neural development. KEY WORDS: NUAK, chick embryo, in situ hybridizationNUAK1 and NUAK2 are members of the novel (Nua) kinases family. Their alternative names include: ARK5 or OMPHK1 for NUAK1; and SNARK or OMPHK2 for NUAK2. They are two of the fourteen known substrates of the serine threonine kinase LKB1 and are part of the AMPK-related protein kinase family (ARK) (Al-Hakim et al., 2005, Hardie and Alessi, 2013, Manning et al., 2002, Suzuki et al., 2003. AMPK is a mammalian homolog of sucrose non-fermentable protein kinase (SNF-1); it is a member of a serine/threonine protein kinase family. Unlike AMPK, which is activated under various stress conditions resulting in decreased ATP concentrations (Scott et al., 2007), ARKs do not have AMP: ATP ratio-sensitive regulatory subunits. Thus, they do not directly participate in adaptive responses to energy balance (Al-Hakim et al., 2005).NUAK1 was first described as supporting AKT-dependent cell survival during nutrient starvation (Suzuki et al., 2003), and has been shown to induce p53 phosphorylation (Hou et al., 2011). NUAK1 expression is now known to be closely associated with metastases, colorectal cancer and is an indicator of poor prognoInt. J. Dev. Biol. 58: 379-384 (2014) sis for glioma (Lu et al., 2013). Recently, it was shown to favor an invasive phenotype in human breast cancer which also depended on AKT signaling. This may be linked to its role in cell adhesion through phosphorylation of the regulatory sub-unit of the myosin light chain 2 (MLC...

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Section: Resultssupporting

confidence: 82%

mentioning

confidence: 99%

Analysis of NUAK1 and NUAK2 expression during early chick development reveals specific patterns in the developing head

Bekri¹,

Billaud²,

Thélu³

2014

Int. J. Dev. Biol.

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“…Also there is experimental mouse evidence showing that teratogen caused apoptosis of the lateral wall musculature is associated with large abdominal wall defects in mice [Wei and Sulik, 1993]. However, it should be kept in mind that there are differences in the early embryology of mouse and human with respect to the relationship of the yolk sac to the embryo and in the process of abdominal wall closure [Hirano et al, 2006]. There are two reasons we have looked to an alternative explanation.…”

Section: What Can Be Summarized and Concluded From An Examination Of mentioning

confidence: 99%

“…There are several animal models that have been referred to as models for human gastroschisis/omphalocele but the animals in fact suffer large ventral wall defects; neither gastroschisis nor true omphalocele [Minsker et al, 1983;Hillebrandt et al, 1998;Hirano et al, 2006;Layne et al, 2001]. The gene Omphk1 is expressed in the epidermis and all tissues of the lateral abdominal wall and in the knockout mouse model there is complete failure of abdominal wall closure [Hirano et al, 2006].…”

Section: What Can Be Summarized and Concluded From An Examination Of mentioning

confidence: 99%

“…The gene Omphk1 is expressed in the epidermis and all tissues of the lateral abdominal wall and in the knockout mouse model there is complete failure of abdominal wall closure [Hirano et al, 2006]. Mice deleted for the Aclp gene, which is widely expressed, including in developing vasculature and dermis, also show large ventral wall defects, and in addition their dermal cells show reduced proliferation in culture [Layne et al, 2001].…”

Section: What Can Be Summarized and Concluded From An Examination Of mentioning

confidence: 99%

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Limb–body wall defect. Is there a defensible hypothesis and can it explain all the associated anomalies?

Hunter

Seaver

Stevenson

2011

American J of Med Genetics Pt A

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Aside from gastroschisis and omphalocele, major defects of the ventral body (thoracoabdominal) wall are relatively uncommon and almost universally lethal. They are most often associated with other anomalies including those of the limbs that may range from amelia to mild positional deformations, unusual craniofacial malformations, and a variety of visceral abnormalities that include the heart, lungs, genitourinary system, and gut. This complex of ventral wall anomalies has been discussed under a broad and changing nomenclature that has included amniotic band disruption complex, amnion rupture sequence, limb-body wall defect (or complex), and simply body wall complex. Three major theories have been suggested to explain this complex: early amnion rupture (operating through uterine pressure and/or disruption by amniotic bands), vascular compromise (primarily hypoperfusion), and an early intrinsic defect of the developing embryo. We present four patients that illustrate the spectrum of ventral body wall defects, and from there critique the current hypotheses of pathogenesis. We conclude that this association of malformations originates as early as the embryonic disc stage, and that some of the observed associated anomalies are secondary complications of the primary disturbance in embryogenesis. We propose a new explanation for the atypical facial clefts and cranial malformations that are often observed.

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Animal models of ventral body wall closure defects: A personal perspective on gastroschisis

Williams

2008

American J of Med Genetics Pt C

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Malformations affecting the ventral body wall comprise one of the leading categories of human birth defects. Gastroschisis is a particularly important body wall closure defect as its incidence is rising worldwide. Although the occurrence of such defects is relatively common their molecular and cellular basis is very poorly understood. A robust animal model system to study the etiology of gastroschisis would be very useful, but several problems currently hamper the identification of such a model. A concerted effort is required to recognize, characterize, and classify ventral body wall defects in animal model species so that progress can be made in determining the mechanisms of ventral body wall closure during human development as well as combating the increased incidence of gastroschisis worldwide. ß

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A new serine/threonine protein kinase,Omphk1, essential to ventral body wall formation

Cited by 24 publications

References 29 publications

Analysis of NUAK1 and NUAK2 expression during early chick development reveals specific patterns in the developing head

Analysis of NUAK1 and NUAK2 expression during early chick development reveals specific patterns in the developing head

Limb–body wall defect. Is there a defensible hypothesis and can it explain all the associated anomalies?

Animal models of ventral body wall closure defects: A personal perspective on gastroschisis

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