Expression of transcription factor HNF-4 in the extraembryonic endoderm, gut, and nephrogenic tissue of the developing mouse embryo: HNF-4 is a marker for primary endoderm in the implanting blastocyst.

Duncan, Stephen A.; Manova, Katia; Chen, William S.; Hoodless, Pamela A.; Weinstein, Daniel C.; Bachvarova, Rosemary F.; Darnell, James

doi:10.1073/pnas.91.16.7598

Cited by 330 publications

(234 citation statements)

References 30 publications

Supporting

Mentioning

225

Contrasting

Unclassified

Order By: Relevance

“…HNF4␣ expression has previously been demonstrated in the pancreas but with unspecified cellular distribution (28,29). To assess the expression of HNF4␣ in the fetal pancreas when the PAX4 gene is actively transcribed, we gauged HNF4␣ mRNA expression by RT-PCR and found that HNF4␣ mRNA peaks in the pancreas at E13.5 (Fig.…”

Section: Resultsmentioning

confidence: 99%

Autoregulation and Maturity Onset Diabetes of the Young Transcription Factors Control the Human PAX4 Promoter

Smith¹,

Watada²,

Scheel³

et al. 2000

Journal of Biological Chemistry

View full text Add to dashboard Cite

During pancreatic development, the paired homeodomain transcription factor PAX4 is required for the differentiation of the insulin-producing beta cells and somatostatin-producing delta cells. To establish the position of PAX4 in the hierarchy of factors controlling islet cell development, we examined the control of the human PAX4 gene promoter. In both cell lines and transgenic animals, a 4.9-kilobase pair region directly upstream of the human PAX4 gene transcriptional start site acts as a potent pancreas-specific promoter. Deletion mapping experiments demonstrate that a 118-base pair region lying approximately 1.9 kilobase pairs upstream of the transcription start site is both necessary and sufficient to direct pancreas-specific expression. Serial deletions through this region reveal the presence of positive elements that bind several pancreatic transcription factors as follows: the POU homeodomain factor HNF1␣, the orphan nuclear receptor HNF4␣, the homeodomain factor PDX1, and a heterodimer composed of two basic helix-loop-helix factors. Interestingly, mutations in the genes encoding four of these factors cause a dominantly inherited form of human diabetes called Maturity Onset Diabetes of the Young. In addition, PAX4 itself has at least two high affinity binding sites within the promoter through which it exerts a strong negative autoregulatory effect. Together, these results suggest a model in which PAX4 expression is activated during pancreatic development by a combination of pancreas-specific factors but is then switched off once PAX4 protein reaches sufficient levels.Organogenesis of the mammalian pancreas and its differentiation into discrete populations of endocrine and exocrine cells depends on the tightly regulated temporal and spatial expression of an array of transcription factors (for reviews see Refs. 1-3). Some of these factors, such as HNF3␤ (4, 5), PDX1 (6, 7), and HLXb9 (8, 9), are involved in the formation and outgrowth of the dorsal and ventral pancreatic buds. Within the forming pancreas, the basic helix-loop-helix transcription factor neurogenin3 functions as a pro-endocrine gene, initiating the program of endocrine differentiation in selected cells (10, 11). The complete differentiation and maturation of the endocrine cells requires additional factors, including neuroD1/BETA2 (12), NKX2.2 (13), ISL1 (14), and PAX6 (2, 15).Once neurogenin3 expression sets a progenitor cell on a course of endocrine differentiation, additional factors are necessary to determine which of the four endocrine cell types it will become. One of these islet cell-type determination factors is the paired homeodomain transcription factor PAX4. PAX4 functions as a potent transcriptional repressor and is expressed only transiently in the fetal pancreas, peaking during the period of beta and delta cell differentiation (16). Mice with a targeted disruption of the pax4 gene have a marked decrease in beta and delta cells with a commensurate increase in alpha cells (17), suggesting that PAX4 functions by repressing the alpha...

show abstract

Section: Resultsmentioning

confidence: 99%

Autoregulation and Maturity Onset Diabetes of the Young Transcription Factors Control the Human PAX4 Promoter

Smith¹,

Watada²,

Scheel³

et al. 2000

Journal of Biological Chemistry

View full text Add to dashboard Cite

show abstract

“…HNF4A is a member of the nuclear receptor family of transcription factors, which is expressed in several tissues, including the liver, gut, kidney and pancreas [43]. Whereas the expression of HNF4A in the liver is mediated by a proximal promoter (P1), its expression in beta cells is driven by an alternative beta cell promoter (P2) located 46 kb upstream of P1 [44,45].…”

Section: Hnf4a Variantsmentioning

confidence: 99%

Common variants in MODY genes increase the risk of gestational diabetes mellitus

et al. 2006

View full text Add to dashboard Cite

“…Compromised function of either parietal or visceral endoderm can result in arrested development at this stage (for review, see Copp 1995; see also Chen et al 1994;Healy et al 1995;Duncan et al 1997). Visceral and parietal endoderm arise from primitive endoderm by -E4.5 in the mouse (Gardner 1983;Duncan et al 1994). Visceral endoderm forms a layer of columnar-shaped cells that surrounds the entire embryo where it secretes important nutrients and filters substances between the maternal and embryonic compartments.…”

Section: Loss Of Gastrulation In a Percentage Of Gata4 Mutant Embryosmentioning

confidence: 99%

Requirement of the transcription factor GATA4 for heart tube formation and ventral morphogenesis.

Molkentin¹,

Lin²,

Duncan³

et al. 1997

Genes Dev.

Self Cite

1,053

773

View full text Add to dashboard Cite

The zinc finger transcription factor GATA4 has been implicated in heart development based on its early expression in precardiogenic splanchnic mesoderm and its ability to activate the expression of a number of cardiac-specific genes. To determine the role of GATA4 in embryogenesis, we generated mice homozygous for a GATA4 null allele. Homozygous GATA4 null mice arrested in development between E7.0 and E9.5 because of severe developmental abnormalities. Mutant embryos most notably lacked a primitive heart tube and foregut and developed partially outside the yolk sac. In the mutants, the two bilaterally symmetric promyocardial primordia failed to migrate ventrally but instead remained lateral and generated two independent heart tubes that contained differentiated cardiomyocytes. We show that these deformities resulted from a general loss in lateral to ventral folding throughout the embryo. GATA4 is most highly expressed within the precardiogenic splanchnic mesoderm at the posterior lip of the anterior intestinal portal, corresponding to the region of the embryo that undergoes ventral fusion. We propose that GATA4 is required for the migration or folding morphogenesis of the precardiogenic splanchnic mesodermal cells at the level of the AIP.

show abstract

Expression of transcription factor HNF-4 in the extraembryonic endoderm, gut, and nephrogenic tissue of the developing mouse embryo: HNF-4 is a marker for primary endoderm in the implanting blastocyst.

Cited by 330 publications

References 30 publications

Autoregulation and Maturity Onset Diabetes of the Young Transcription Factors Control the Human PAX4 Promoter

Autoregulation and Maturity Onset Diabetes of the Young Transcription Factors Control the Human PAX4 Promoter

Common variants in MODY genes increase the risk of gestational diabetes mellitus

Requirement of the transcription factor GATA4 for heart tube formation and ventral morphogenesis.

Contact Info

Product

Resources

About