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Results highlight the possibility that Ptf1a may act as an important transcription factor for enteric neuron development.
In ptf1a haploinsufficiency, more ptf1a-lineage-labeled cells are traced into the pancreatic Notch (show NOTCH1 Proteins)-responsive cell and endocrine compartments. More reduction of ptf1a gene dosage converts pancreatic progenitor cells to non-pancreatic cell fates.
Autoregulation of ptf1a is absolutely required for exocrine pancreas formation.
Postembryonic antagonism of Ptf1a, a master regulator of pancreatic development and acinar cell fate specification, induced expression of endocrine genes including insulin (show INS Proteins) in the exocrine compartment. Induced insulin (show INS Proteins)+ cells are derived from acinar cells.
The timing of Ptf1a expression suggests that it is involved in the very early stages or steps in the differentiation of amacrine cells, which can be seen to rapidly diversify into a large number of subtypes.
Ptf1 function is inhibited by notch (show NOTCH1 Proteins)
We propose that low levels of Ptf1a promote endocrine fate, whereas high levels repress endocrine fate and promote exocrine fate.
Exocrine differentiation and proliferation factor (exdpf) is a direct target gene of pancreas-specific transcription factor 1a (Ptf1a).
Xenopus Ptf1a is essential for the initial specification of both endocrine and exocrine cells during normal pancreas development.
Ptf1a overexpression leads to an increased ratio of GABAergic subtypes among the whole amacrine and horizontal cell population, highlighting its instructive capacity to promote this specific subtype of inhibitory neurons
analysis of the gene regulatory network activated by Ptf1a in early pancreas development;results revealed that Ptf1a regulates genes with a wide variety of functions, providing insight into the complexity of the regulatory network required for pancreas specification
Study describes the wide range of gene control by PTF1A that maintains the specific characteristics of pancreatic acinar cell identity and differentiation. PTF1A controls the pancreatic acinar transcription program by direct action at a thousand genes and in collaboration with other less cell type-restricted factors to ensure acinar cell homeostasis and to suppress other cell-type-specific programs.
Data show isolated Pancreatic Aplasia Due to a Hypomorphic PTF1A Mutation
The results of this study suggested Ptf1a-dependent cell-fate misspecification as a novel mechanism of human brainstem pathology.
PTF1A enhancer mutations have been shown to cause neonatal diabetes associated with pancreatic agenesis
Loss of Ptf1a alone is sufficient to induce acinar-to-ductal metaplasia, potentiate inflammation, and induce a KRAS-permissive, pancreatic ductal adenocarcinoma-like gene expression profile.
The results of the present study do not support the hypothesis that high penetrant mutations in these regions of PTF1A are involved in the development of human VATER/VACTERL association or NTDs
ata indicate that E3 ubiquitin ligase (show MUL1 Proteins) thyroid hormone receptor (show THRA Proteins)-interacting protein (show RIPK1 Proteins) 12 (TRIP12) promotes proteasomal degradation of pancreas transcription factor 1a (PTF1a)and regulates PTF1a activities.
Recessive mutations in a distal PTF1A enhancer cause isolated pancreatic agenesis.
ICAT (show CTNNBIP1 Proteins) is a novel Ptf1a interactor that regulates pancreatic acinar differentiation and displays altered expression.
ptf1a functions as a "pancreatic determiner".
Ptf1a is regulated by active and repressive inputs integrated through multiple sequence elements within a highly conserved sequence downstream of the Ptf1a gene.
the Tfap2a (show TFAP2A Proteins) and Tfap2b (show TFAP2B Proteins) transcription factors were identified as two major downstream effectors of Ptf1a.
This study demonstrated that the transcription factor Ptf1a is capable of cell autonomously redirecting cortical pyramidal cell identity toward an inhibitory peptidergic fate.
We provide strong evidence for spatiotemporally context-dependent activity of Ptf1a as a potent gain-of-function trigger of pro-pancreatic commitment.
Data suggest the role of pancreas-specific transcription factor 1a (PTF1a) in pancreas development in directing differentiation of embryonic stem cells (ESCs (show NR2E3 Proteins)) to endocrine cells.
GABAergic inducing activity of Ascl1 (show ASCL1 Proteins) requires the direct transcriptional regulation of Ptf1a.
Ascl1 (show ASCL1 Proteins) and Ptf1a directly regulate distinct homeodomain transcription factors that specify excitatory or inhibitory neuronal fates.
These data identify Ptf1a as the first gene involved in the segregation of the cerebellum from the more ventral brainstem.
The results of this study suggested that Ptf1a specify spatial identities of cerebellar neuron progenitors in the neuroepithelium, leading to appropriate production of GABAergic and glutamatergic neurons, respectively.
The results support a model whereby Ptf1a directs distinct gene expression programs that are established by the interplay of chromatin accessibility, collaborating transcription factors, and the DNA motifs within tissue-specific regulatory enhancers.
This gene encodes a protein that is a component of the pancreas transcription factor 1 complex (PTF1) and is known to have a role in mammalian pancreatic development. The protein plays a role in determining whether cells allocated to the pancreatic buds continue towards pancreatic organogenesis or revert back to duodenal fates. The protein is thought to be involved in the maintenance of exocrine pancreas-specific gene expression including elastase 1 and amylase. Mutations in this gene cause cerebellar agenesis and loss of expression is seen in ductal type pancreas cancers.
pancreas specific transcription factor, 1a
, bHLH transcription factor p48
, pancreas transcription factor 1 subunit alpha
, pancreas-specific transcription factor 1a
, Pancreas-specific transcription factor 1a
, transcription factor Ptf1a/p48
, class A basic helix-loop-helix protein 29
, class II bHLH protein PTF1A
, exocrine pancreas-specific transcription factor p48
, p48 DNA-binding subunit of transcription factor PTF1
, pancreas transcription factor1 p48 subunit