All hormone-producing cell types of the pituitary intermediate and anterior lobes derive from prop1-expressing progenitors

Mutations in PROP1, the most common known cause of combined pituitary hormone deficiency in humans, can result in the progressive loss of all hormones of the pituitary anterior lobe. In mice, Prop1 mutations result in the failure to initiate transcription of Pou1f1 (also known as Pit1) and lack somatotropins, lactotropins, and thyrotropins. The basis for this species difference is unknown. We hypothesized that Prop1 is expressed in a progenitor cell that can develop into all anterior lobe cell types, and not just the somatotropes, thyrotropes, and lactotropes, which are collectively known as the PIT1 lineage. To test this idea, we produced a transgenic Prop1-cre mouse line and conducted lineage-tracing experiments of Prop1-expressing cells. The results reveal that all hormone-secreting cell types of both the anterior and intermediate lobes are descended from Prop1-expressing progenitors. The Prop1-cre mice also provide a valuable genetic reagent with a unique spatial and temporal expression for generating tissue-specific gene rearrangements early in pituitary gland development. We also determined that the minimal essential sequences for reliable Prop1 expression lie within 10 kilobases of the mouse gene and demonstrated that human PROP1 can substitute functionally for mouse Prop1. These studies enhance our understanding of the pathophysiology of disease in patients with PROP1 mutations.Fil: Davis, Shannon W.. University of South Carolina; Estados UnidosFil: Keisler, Jessica L.. University of South Carolina; Estados UnidosFil: Pérez Millán, María Inés. University of Michigan; Estados Unidos. Consejo Nacional de Investigaciones Científicas y Técnicas; ArgentinaFil: Schade, Vanessa. University of Michigan; Estados UnidosFil: Camper, Sally A.. University of Michigan; Estados Unido

Embryonic Development of the Deer Mouse, Peromyscus maniculatus.

Deer mice, or Peromyscus maniculatus, are an emerging model system for use in biomedicine. P. maniculatus are similar in appearance to laboratory mice, Mus musculus, but are more closely related to hamsters than to Mus. The laboratory strains of Peromyscus have captured a high degree of the genetic variability observed in wild populations, and are more similar to the genetic variability observed in humans than are laboratory strains of Mus. The Peromyscus Genetic Stock Center at the University of South Carolina maintains several lines of Peromyscus harboring mutations that result in developmental defects. We present here a description of P. maniculatus development from gastrulation to late gestation to serve as a guide for researchers interested in pursuing developmental questions in Peromyscus

Ear development in <i>P</i>. <i>maniculatus</i> embryos from e11.5 to e21.5.

<p>(A) e11.5 embryo. Arrow indicates invaginating otic placode. (B) e12.5 embryo. (C) e13.5 embryo. Dotted line indicates otic placode, which has become internalized. (D) e14.5 embryo. Dotted line indicates otic placode, which has become internalized. (E) e15.5 embryo, dorsal view. Arrow indicates the pinna. (F) e16.5 embryo. Arrow indicates the auditory meatus. (G) e17.5 embryo. (H) e18.5 embryo. (I) e19.5 embryo. (J) e20.5 embryo. (K) e21.5 embryo. Scale bars in A–D equal 100 μm. Scale bars in E–K equal 1 mm.</p

Variability between individuals of the same litter and between litters of <i>P</i>. <i>maniculatus</i> embryos.

<p>(A) One litter of four e11.5 embryos. (B) Two litters of three e12.5 embryos, separated into rows. (C) One litter of four e13.5 embryos. All scale bars equal 1 mm.</p

Hindlimb development in P. <i>maniculatus</i> embryos from e12.5 to e21.5.

<p>(A) e12.5 embryo, lateral view of right side. Arrow indicates right hindlimb bud. (B) e13.5 embryo, dorsal view. Arrow indicates right hindlimb bud. (C–J) Lateral views of left forelimb. (C) e14.5 embryo. (D) e15.5 embryo. (E) e16.5 embryo. Arrow indicates digit condensation. (F) e17.5 embryo. Arrow indicates interdigital tissue. (G) e18.5 embryo. Arrow indicates developing ankle. (H) e19.5 embryo. (I) e20.5 embryo. Arrow indicates forming nail. (J) e21.5 embryo. All scale bars equal 1 mm.</p

Dorsal views of e10.5 to e16.5 <i>P</i>. <i>maniculatus</i> embryos.

<p>(A) e10.5 embryo. (B) e11.5 embryo. Arrow indicates division between the mesencephalon and rhombencephalon. (C) e12.5 embryo. Arrow indicates division between the mesencephalon and rhombencephalon. (D) e13.5 embryo. (E) e14.5 embryo. Arrow indicates the rhombic lip. (F) e15.5 embryo. Arrow indicates the rhombic lip. (G) e16.5 embryo. Scale bars in A and B equal 100 μm. Scale bars in C–G equal 1 mm.</p

Eye development in <i>P</i>. <i>maniculatus</i> embryos from e11.5 to e19.5.

<p>(A) e11.5 embryo. Arrow indicates the boundary between the optic cup and the invaginating optic placode. (B) e12.5 embryo. (C) e13.5 embryo. Arrow indicates first pigmentation in the RPE. (D) e14.5 embryo. Arrow indicates the choroidal fissure. (E) e15.5 embryo. (F) e16.5 embryo. Arrow indicates the forming eye lid. (G) e17.5 embryo. (H) e18.5 embryo. (I) e19.5 embryo. Arrow indicates the fused eye lids. All scale bars equal 100 μm.</p

Frontal views of e10.5 to e21.5 <i>P</i>. <i>maniculatus</i> embryos.

<p>(A) e10.5 embryo. Arrow indicates the first pair of somites. (B) e11.5 embryo. Arrows indicate divisions between the telencephalon and diencephalon (lower) and diencephalon and mesencephalon (upper). (C) e12.5 embryo. (D) e13.5 embryo. Arrow indicates olfactory pit. (E) e14.5 embryo. (F) e15.5 embryo. (G) e16.5 embryo. Arrow indicates the prospective area of the forming vibrissae. (H) e17.5 embryo. (I) e18.5 embryo. Arrow indicates the prospective area of the forming vibrissae. (J) e19.5 embryo. (K) e20.5 embryo. (L) e21.5 embryo. Scale bars in A and B equal 100 μm. Scale bars in C–L equal 1 mm.</p

Pharyngeal arch development in <i>P</i>. <i>maniculatus</i> embryos from e11.5 to e15.5.

<p>(A) e11.5 embryo. Arrow indicates the first pharyngeal arch. (B) e12.5 embryo. Arrow indicates the second pharyngeal arch. Asterisk marks the division between maxilla and mandible. (C) e13.5 embryo. Arrow indicates the third pharyngeal arch. (D) e14.5 embryo. (E) e15.5 embryo. Scale bars in A and B equal 100 μm. Scale bars in C–E equal 1 mm.</p