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1.
bioRxiv ; 2024 Sep 16.
Artigo em Inglês | MEDLINE | ID: mdl-39345443

RESUMO

Normal placental development and angiogenesis are crucial for fetal growth and maternal health during pregnancy. However, molecular regulation of placental angiogenesis has been difficult to study due to a lack of specific genetic tools that isolate the placenta from the embryo and yolk sac. To address this gap in knowledge we recently developed Hoxa13 Cre mice in which Cre is expressed in allantois-derived cells, including placental endothelial and stromal cells. Mice lacking the transcriptional regulators Yes-associated protein (YAP) and PDZ-binding motif (TAZ) in allantois-derived cells exhibit embryonic lethality at midgestation with compromised placental vasculature. snRNA-seq analysis revealed transcriptional changes in placental stromal cells and endothelial cells. YAP/TAZ mutants exhibited significantly reduced placental stromal cells prior to the endothelial architectural change, highlighting the role of these cells in placental vascular growth. These results reveal a central role for YAP/TAZ signaling during placental vascular growth and implicate Hoxa13 -derived placental stromal cells as a critical component of placental vascularization.

2.
JAMA Netw Open ; 5(9): e2233080, 2022 09 01.
Artigo em Inglês | MEDLINE | ID: mdl-36149654

RESUMO

Importance: Despite being one of the fastest-growing populations in the US, the Asian American population is often misrepresented in and omitted from health research and policy debate. There is a current lack of understanding of how Asian American populations are portrayed in medical school curricula. Objective: To assess how Asian American populations and their subgroups are represented in medical school curricula. Design, Setting, and Participants: In this qualitative study, the content of 632 lectures from all 19 courses of the preclinical curriculum at a single US institution from the academic year 2020 to 2021 was analyzed to identify and characterize unique mentions of race and ethnicity as well as granular ethnicity. Among the 632 lectures, we identified 256 nonrepetitive, unique mentions of race and ethnicity or granular ethnicity. These unique mentions were coded and analyzed for emerging patterns of use. Main Outcomes and Measures: Study outcomes included (1) the frequency of specific racial and ethnic categories mentioned in the curriculum, (2) the relative proportion of mentions of race and ethnicity that involved or included Asian American data by courses and context, and (3) key themes representing emerging patterns found from qualitative analysis of curriculum content for mentions of Asian American populations or lack thereof. Results: Among the 632 lectures, 256 nonrepetitive mentions of race and ethnicity or granular ethnicity were identified; of these, Asian American populations and/or their subgroups were mentioned in 79 of the instances (30.9%). The most common terms used to denote Asian American populations were Asian, with 36 mentions (45.6%); followed by Japanese, with 10 mentions (12.7%); and Chinese, with 8 mentions (10.1%). Overall, there were 26 mentions (10.2%) of American Indian or Alaska Native populations, 12 mentions (4.7%) of Asian and Pacific Islander or Asian American and Pacific Islander populations, 67 mentions (26.2%) of Asian or Asian American populations, 143 mentions (55.9%) of Black or African American populations, 62 mentions (24.2%) of Hispanic or Latino populations, 4 mentions (1.6%) of Native Hawaiian or Pacific Islander populations, and 154 mentions (60.2%) of White populations. During the analysis of the curriculum for representation of Asian American populations, the following 5 key themes emerged from the data: (1) omission, (2) aggregation, (3) inconsistent categorization, (4) misidentification of granular ethnicity, and (5) association of race and ethnicity with disease. Conclusions and Relevance: This qualitative study suggests that the curriculum from a single US medical school largely mirrors the inappropriate use of race and ethnicity found in published health literature and clinical guidelines. Solutions with long-term results will require collaboration among diverse groups of interest to adopt inclusive research programs and design. Such solutions could better equip students in combating race-based medicine and could promote community outreach programs built based on trust.


Assuntos
Asiático , Faculdades de Medicina , Currículo , Etnicidade , Hispânico ou Latino , Humanos
3.
J Comp Neurol ; 529(7): 1293-1307, 2021 05 01.
Artigo em Inglês | MEDLINE | ID: mdl-32869305

RESUMO

In vertebrate animals, motor and sensory efferent neurons carry information from the central nervous system (CNS) to peripheral targets. These two types of efferent systems sometimes bear a close resemblance, sharing common segmental organization, axon pathways, and chemical messengers. Here, we focus on the development of the octavolateral efferent neurons (OENs) and their interactions with the closely-related facial branchiomotor neurons (FBMNs) in zebrafish. Using live-imaging approaches, we investigate the birth, migration, and projection patterns of OENs. We find that OENs are born in two distinct groups: a group of rostral efferent neurons (RENs) that arises in the fourth segment, or rhombomere (r4), of the hindbrain and a group of caudal efferent neurons (CENs) that arises in r5. Both RENs and CENs then migrate posteriorly through the hindbrain between 18 and 48 hrs postfertilization, alongside the r4-derived FBMNs. Like the FBMNs, migration of the r4-derived RENs depends on function of the segmental identity gene hoxb1a; unlike the FBMNs, however, both OEN populations move independently of prickle1b. Further, we investigate whether the previously described "pioneer" neuron that leads FBMN migration through the hindbrain is an r4-derived FBMN/REN or an r5-derived CEN. Our experiments verify that the pioneer is an r4-derived neuron and reaffirm its role in leading FBMN migration across the r4/5 border. In contrast, the r5-derived CENs migrate independently of the pioneer. Together, these results indicate that the mechanisms OENs use to navigate the hindbrain differ significantly from those employed by FBMNs.


Assuntos
Movimento Celular/fisiologia , Neurogênese/fisiologia , Neurônios Eferentes/fisiologia , Rombencéfalo/citologia , Rombencéfalo/fisiologia , Animais , Peixe-Zebra
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