Distinct Actions of<i>Emx1</i>,<i>Emx2</i>, and<i>Pax6</i>in Regulating the Specification of Areas in the Developing Neocortex
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Bibliographic record
Abstract
The mammalian neocortex is organized into subdivisions referred to as areas that are distinguished from one another by differences in architecture, axonal connections, and function. The transcription factors EMX1, EMX2, and PAX6 have been proposed to regulate arealization. <i>Emx1</i> and <i>Emx2</i> are expressed by progenitor cells in a low rostrolateral to high caudomedial gradient across the embryonic neocortex, and <i>Pax6</i> is expressed in a high rostrolateral to low caudomedial gradient. Recent evidence has suggested that EMX2 and PAX6 have a role in the genetic regulation of arealization. Here we use a panel of seven genes (<i>Cad6</i>, <i>Cad8</i>, <i>Id2</i>,<i>RZRβ</i>, <i>p75</i>, <i>EphA7</i>, and <i>ephrin-A5</i>) representative of a broad range of proteins as complementary markers of positional identity to obtain a more thorough assessment of the suggested roles for EMX2 and PAX6 in arealization, and in addition to assess the proposed but untested role for EMX1 in arealization. Orderly changes in the size and positioning of domains of marker expression in <i>Emx2</i> and<i>Pax6</i> mutants strongly imply that rostrolateral areas (motor and somatosensory) are expanded, whereas caudomedial areas (visual) are reduced in <i>Emx2</i> mutants and that opposite effects occur in <i>Pax6</i> mutants, consistent with their opposing gradients of expression. In contrast, patterns of marker expression, as well as the distribution of area-specific thalamocortical projections, appear normal in <i>Emx1</i>mutants, indicating that they do not exhibit changes in arealization. This lack of a defined role for EMX1 in arealization is supported by our finding of similar shifts in patterns of marker expression in<i>Emx1; Emx2</i> double mutants as in <i>Emx2</i> mutants. Thus, our findings indicate that EMX2 and PAX6 regulate, in opposing manners, arealization of the neocortex and impart positional identity to cortical cells, whereas EMX1 appears not to have a role in this process.
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Full frame distilled prediction
Teacher imitationNot calibrated prevalence, not ground truth. Human validation pending. Learned from the 10,348 direct Codex labels and 10,348 direct Gemma labels. Candidate is the union of thresholded teacher heads; consensus is their intersection. These outputs are machine_predicted_unvalidated and are not human labels or direct frontier model labels.
Codex and Gemma teacher scores by category
| Category | Codex | Gemma |
|---|---|---|
| Metaresearch | 0.001 | 0.000 |
| Meta-epidemiology (narrow) | 0.000 | 0.000 |
| Meta-epidemiology (broad) | 0.000 | 0.000 |
| Bibliometrics | 0.000 | 0.000 |
| Science and technology studies | 0.000 | 0.000 |
| Scholarly communication | 0.000 | 0.000 |
| Open science | 0.000 | 0.000 |
| Research integrity | 0.000 | 0.000 |
| Insufficient payload (model declined to judge) | 0.000 | 0.000 |
Machine scores (provisional)
The two teacher heads of the student model, read on this work. A score orders the frame for review; it never asserts a category, and the validation status ships verbatim with every row.
Baseline scores from an immature model (maturity gate not passed, 7 training rounds). Scores rank; they never assert a category.
score_only:v0-immature-baseline · verbatim from the scoring run: score_only means the number may rank works, and no category label ships from it